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PDBsum entry 1p9u
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Hydrolase/hydrolase inhibitor PDB id
1p9u

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
(+ 0 more) 299 a.a. *
Ligands
VAL-ASN-SER-THR-
LEU-GLN-0QE ×2
SO4 ×24
MRD ×4
Waters ×924
* Residue conservation analysis
PDB id:
1p9u
Name: Hydrolase/hydrolase inhibitor
Title: Coronavirus main proteinase (3clpro) structure: basis for design of anti-sars drugs
Structure: Putative coronavirus nsp2 (3cl-pro). Chain: a, b, c, d, e, f. Fragment: tgev main proteinase. Engineered: yes. Phq-vnstlq-chloromethylketone inhibitor. Chain: g, h. Engineered: yes
Source: Transmissible gastroenteritis virus. Organism_taxid: 11149. Gene: orf1a. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: substrate-analog
Biol. unit: Monomer (from PQS)
Resolution:
2.37Å     R-factor:   0.191     R-free:   0.234
Authors: K.Anand,J.Ziebuhr,P.Wadhwani,J.R.Mesters,R.Hilgenfeld
Key ref:
K.Anand et al. (2003). Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science, 300, 1763-1767. PubMed id: 12746549 DOI: 10.1126/science.1085658
Date:
12-May-03     Release date:   20-May-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0C6Y5  (R1AB_CVPPU) -  Replicase polyprotein 1ab from Porcine transmissible gastroenteritis coronavirus (strain Purdue)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		6684 a.a.
299 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.1.1.57  - methyltransferase cap1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H+
5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA
 + S-adenosyl-L-methionine
 = 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA
 + S-adenosyl-L-homocysteine
 + H(+)
   Enzyme class 3: E.C.2.7.7.48  - RNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
RNA(n)
 + ribonucleoside 5'-triphosphate
 = RNA(n+1)
 + diphosphate
   Enzyme class 4: E.C.2.7.7.50  - mRNA guanylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a 5'-end diphospho-ribonucleoside in mRNA + GTP + H+ = a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphate
5'-end diphospho-ribonucleoside in mRNA
 + GTP
 + H(+)
 = 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA
 + diphosphate
   Enzyme class 5: E.C.3.1.13.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 6: E.C.3.4.19.12  - ubiquitinyl hydrolase 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
   Enzyme class 7: E.C.3.4.22.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 8: E.C.3.6.4.12  - Dna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
   Enzyme class 9: E.C.3.6.4.13  - Rna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
   Enzyme class 10: E.C.4.6.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1126/science.1085658 Science 300:1763-1767 (2003)
PubMed id: 12746549  
 
 
Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.
K.Anand, J.Ziebuhr, P.Wadhwani, J.R.Mesters, R.Hilgenfeld.
 
  ABSTRACT  
 
A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Dimer of HCoV Mpro. The N-terminal residues of each chain squeeze between domains II and III of the parent monomer and domain II of the other monomer. N and C termini are labeled by cyan and magenta spheres and the letters N and C, respectively. 		Figure 4.
Fig. 4. Derivatives of the antirhinoviral drug AG7088 should inhibit coronavirus Mpros. A superimposition (stereo image) of the substrate-binding regions of TGEV Mpro (marine) in complex with the hexapeptidyl CMK inhibitor (red) and HRV2 3C^pro (green) in complex with the inhibitor AG7088 (yellow) is shown.
 
  The above figures are reprinted by permission from the AAAs: Science (2003, 300, 1763-1767) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21324206 H.H.Liao, Y.C.Wang, M.C.Chen, H.Y.Tsai, J.Lin, S.T.Chen, G.J.Tsay, and S.L.Cheng (2011).
Down-regulation of granulocyte-macrophage colony-stimulating factor by 3C-like proteinase in transfected A549 human lung carcinoma cells.
  BMC Immunol, 12, 16.  
21338626 Y.Kumaki, M.K.Wandersee, A.J.Smith, Y.Zhou, G.Simmons, N.M.Nelson, K.W.Bailey, Z.G.Vest, J.K.Li, P.K.Chan, D.F.Smee, and D.L.Barnard (2011).
Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin.
  Antiviral Res, 90, 22-32.  
21087086 D.N.Okamoto, L.C.Oliveira, M.Y.Kondo, M.H.Cezari, Z.Szeltner, T.Juhász, M.A.Juliano, L.Polgár, L.Juliano, and I.E.Gouvea (2010).
Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding effects in the milieu composition.
  Biol Chem, 391, 1461-1468.  
20021285 H.M.Wang, and P.H.Liang (2010).
Picornaviral 3C protease inhibitors and the dual 3C protease/coronaviral 3C-like protease inhibitors.
  Expert Opin Ther Pat, 20, 59-71.  
  20352074 M.Indarte, Y.Liu, J.D.Madura, and C.K.Surratt (2010).
Receptor-Based Discovery of a Plasmalemmal Monoamine Transporter Inhibitor via High Throughput Docking and Pharmacophore Modeling.
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20484504 M.Raaben, C.C.Posthuma, M.H.Verheije, E.G.te Lintelo, M.Kikkert, J.W.Drijfhout, E.J.Snijder, P.J.Rottier, and C.A.de Haan (2010).
The ubiquitin-proteasome system plays an important role during various stages of the coronavirus infection cycle.
  J Virol, 84, 7869-7879.  
20587646 M.Y.Tsai, W.H.Chang, J.Y.Liang, L.L.Lin, G.G.Chang, and H.P.Chang (2010).
Essential covalent linkage between the chymotrypsin-like domain and the extra domain of the SARS-CoV main protease.
  J Biochem, 148, 349-358.  
21119764 R.Giegé, and C.Sauter (2010).
Biocrystallography: past, present, future.
  HFSP J, 4, 109-121.  
20504120 R.N.Kostoff (2010).
The highly cited SARS research literature.
  Crit Rev Microbiol, 36, 299-317.  
20444893 S.Fang, H.Shen, J.Wang, F.P.Tay, and D.X.Liu (2010).
Functional and genetic studies of the substrate specificity of coronavirus infectious bronchitis virus 3C-like proteinase.
  J Virol, 84, 7325-7336.  
19144641 C.C.Lee, C.J.Kuo, T.P.Ko, M.F.Hsu, Y.C.Tsui, S.C.Chang, S.Yang, S.J.Chen, H.C.Chen, M.C.Hsu, S.R.Shih, P.H.Liang, and A.H.Wang (2009).
Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds.
  J Biol Chem, 284, 7646-7655.
PDB codes: 2ztx 2zty 2ztz 2zu1 2zu2 2zu3 2zu4 2zu5
19622868 I.Manolaridis, J.A.Wojdyla, S.Panjikar, E.J.Snijder, A.E.Gorbalenya, H.Berglind, P.Nordlund, B.Coutard, and P.A.Tucker (2009).
Structure of the C-terminal domain of nsp4 from feline coronavirus.
  Acta Crystallogr D Biol Crystallogr, 65, 839-846.
PDB code: 3gzf
19436709 J.Tan, C.Vonrhein, O.S.Smart, G.Bricogne, M.Bollati, Y.Kusov, G.Hansen, J.R.Mesters, C.L.Schmidt, and R.Hilgenfeld (2009).
The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes.
  PLoS Pathog, 5, e1000428.
PDB codes: 2w2g 2wct
19208150 K.Phakthanakanok, K.Ratanakhanokchai, K.L.Kyu, P.Sompornpisut, A.Watts, and S.Pinitglang (2009).
A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism.
  BMC Bioinformatics, 10, S48.  
19319935 N.Zhong, S.Zhang, F.Xue, X.Kang, P.Zou, J.Chen, C.Liang, Z.Rao, C.Jin, Z.Lou, and B.Xia (2009).
C-terminal domain of SARS-CoV main protease can form a 3D domain-swapped dimer.
  Protein Sci, 18, 839-844.
PDB codes: 2k7x 3ebn
19430490 S.Perlman, and J.Netland (2009).
Coronaviruses post-SARS: update on replication and pathogenesis.
  Nat Rev Microbiol, 7, 439-450.  
19261195 X.Tang, G.Li, N.Vasilakis, Y.Zhang, Z.Shi, Y.Zhong, L.F.Wang, and S.Zhang (2009).
Differential stepwise evolution of SARS coronavirus functional proteins in different host species.
  BMC Evol Biol, 9, 52.  
19177346 Y.Piotrowski, G.Hansen, A.L.Boomaars-van der Zanden, E.J.Snijder, A.E.Gorbalenya, and R.Hilgenfeld (2009).
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PDB codes: 3ejf 3ejg 3eke
19875857 Y.Wang, L.Y.Wu, J.H.Zhang, Z.W.Zhan, X.S.Zhang, and L.Chen (2009).
Evaluating protein similarity from coarse structures.
  IEEE/ACM Trans Comput Biol Bioinform, 6, 583-593.  
18987156 Y.Xu, L.Cong, C.Chen, L.Wei, Q.Zhao, X.Xu, Y.Ma, M.Bartlam, and Z.Rao (2009).
Crystal structures of two coronavirus ADP-ribose-1''-monophosphatases and their complexes with ADP-Ribose: a systematic structural analysis of the viral ADRP domain.
  J Virol, 83, 1083-1092.
PDB codes: 3ewo 3ewp 3ewq 3ewr
18427249 A.Golda, and K.Pyrc (2008).
Recent antiviral strategies against human coronavirus-related respiratory illnesses.
  Curr Opin Pulm Med, 14, 248-253.  
18796354 A.K.Ghosh, G.Gong, V.Grum-Tokars, D.C.Mulhearn, S.C.Baker, M.Coughlin, B.S.Prabhakar, K.Sleeman, M.E.Johnson, and A.D.Mesecar (2008).
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  Bioorg Med Chem Lett, 18, 5684-5688.  
18054092 B.Canard, J.S.Joseph, and P.Kuhn (2008).
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  Antiviral Res, 78, 47-50.  
17931870 C.Niu, J.Yin, J.Zhang, J.C.Vederas, and M.N.James (2008).
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  Bioorg Med Chem, 16, 293-302.  
18550673 I.Robel, J.Gebhardt, J.R.Mesters, A.Gorbalenya, B.Coutard, B.Canard, R.Hilgenfeld, and J.Rohayem (2008).
Functional characterization of the cleavage specificity of the sapovirus chymotrypsin-like protease.
  J Virol, 82, 8085-8093.  
18827877 J.Pan, X.Peng, Y.Gao, Z.Li, X.Lu, Y.Chen, M.Ishaq, D.Liu, M.L.Dediego, L.Enjuanes, and D.Guo (2008).
Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.
  PLoS ONE, 3, e3299.  
18385240 J.S.Sparks, E.F.Donaldson, X.Lu, R.S.Baric, and M.R.Denison (2008).
A novel mutation in murine hepatitis virus nsp5, the viral 3C-like proteinase, causes temperature-sensitive defects in viral growth and protein processing.
  J Virol, 82, 5999-6008.  
18305031 J.Shi, J.Sivaraman, and J.Song (2008).
Mechanism for controlling the dimer-monomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3C-like protease.
  J Virol, 82, 4620-4629.
PDB code: 2qcy
18156685 M.Bartlam, X.Xue, and Z.Rao (2008).
The search for a structural basis for therapeutic intervention against the SARS coronavirus.
  Acta Crystallogr A, 64, 204-213.  
  19203466 M.R.Suresh, P.K.Bhatnagar, and D.Das (2008).
Molecular targets for diagnostics and therapeutics of severe acute respiratory syndrome (SARS-CoV).
  J Pharm Pharm Sci, 11, 1s.  
18305043 N.Zhong, S.Zhang, P.Zou, J.Chen, X.Kang, Z.Li, C.Liang, C.Jin, and B.Xia (2008).
Without its N-finger, the main protease of severe acute respiratory syndrome coronavirus can form a novel dimer through its C-terminal domain.
  J Virol, 82, 4227-4234.  
18562531 Q.Zhao, S.Li, F.Xue, Y.Zou, C.Chen, M.Bartlam, and Z.Rao (2008).
Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1.
  J Virol, 82, 8647-8655.
PDB code: 3d23
17397959 R.L.Graham, J.S.Sparks, L.D.Eckerle, A.C.Sims, and M.R.Denison (2008).
SARS coronavirus replicase proteins in pathogenesis.
  Virus Res, 133, 88.  
18611220 U.Bacha, J.Barrila, S.B.Gabelli, Y.Kiso, L.Mario Amzel, and E.Freire (2008).
Development of broad-spectrum halomethyl ketone inhibitors against coronavirus main protease 3CL(pro).
  Chem Biol Drug Des, 72, 34-49.
PDB code: 3d62
18094151 X.Xue, H.Yu, H.Yang, F.Xue, Z.Wu, W.Shen, J.Li, Z.Zhou, Y.Ding, Q.Zhao, X.C.Zhang, M.Liao, M.Bartlam, and Z.Rao (2008).
Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design.
  J Virol, 82, 2515-2527.
PDB codes: 2q6d 2q6f 2q6g
18406349 Y.Kumaki, C.W.Day, M.K.Wandersee, B.P.Schow, J.S.Madsen, D.Grant, J.P.Roth, D.F.Smee, L.M.Blatt, and D.L.Barnard (2008).
Interferon alfacon 1 inhibits SARS-CoV infection in human bronchial epithelial Calu-3 cells.
  Biochem Biophys Res Commun, 371, 110-113.  
19649165 A.K.Ghosh, K.Xi, M.E.Johnson, S.C.Baker, and A.D.Mesecar (2007).
Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy.
  Annu Rep Med Chem, 41, 183-196.  
17855091 A.K.Ghosh, K.Xi, V.Grum-Tokars, X.Xu, K.Ratia, W.Fu, K.V.Houser, S.C.Baker, M.E.Johnson, and A.D.Mesecar (2007).
Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.
  Bioorg Med Chem Lett, 17, 5876-5880.
PDB code: 2qiq
17520018 A.von Brunn, C.Teepe, J.C.Simpson, R.Pepperkok, C.C.Friedel, R.Zimmer, R.Roberts, R.Baric, and J.Haas (2007).
Analysis of intraviral protein-protein interactions of the SARS coronavirus ORFeome.
  PLoS ONE, 2, e459.  
17407183 C.C.Lai, M.J.Jou, S.Y.Huang, S.W.Li, L.Wan, F.J.Tsai, and C.W.Lin (2007).
Proteomic analysis of up-regulated proteins in human promonocyte cells expressing severe acute respiratory syndrome coronavirus 3C-like protease.
  Proteomics, 7, 1446-1460.  
17428870 E.F.Donaldson, R.L.Graham, A.C.Sims, M.R.Denison, and R.S.Baric (2007).
Analysis of murine hepatitis virus strain A59 temperature-sensitive mutant TS-LA6 suggests that nsp10 plays a critical role in polyprotein processing.
  J Virol, 81, 7086-7098.  
17142288 H.P.Chang, C.Y.Chou, and G.G.Chang (2007).
Reversible unfolding of the severe acute respiratory syndrome coronavirus main protease in guanidinium chloride.
  Biophys J, 92, 1374-1383.  
  17183167 J.Li, W.Shen, M.Liao, and M.Bartlam (2007).
Preliminary crystallographic analysis of avian infectious bronchitis virus main protease.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 24-26.  
17251282 J.Ziebuhr, B.Schelle, N.Karl, E.Minskaia, S.Bayer, S.G.Siddell, A.E.Gorbalenya, and V.Thiel (2007).
Human coronavirus 229E papain-like proteases have overlapping specificities but distinct functions in viral replication.
  J Virol, 81, 3922-3932.  
17083088 K.Zheng, G.Ma, J.Zhou, M.Zen, W.Zhao, Y.Jiang, Q.Yu, and J.Feng (2007).
Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.
  Proteins, 66, 467-479.  
17680348 M.Bartlam, Y.Xu, and Z.Rao (2007).
Structural proteomics of the SARS coronavirus: a model response to emerging infectious diseases.
  J Struct Funct Genomics, 8, 85-97.  
17855519 M.Oostra, E.G.te Lintelo, M.Deijs, M.H.Verheije, P.J.Rottier, and C.A.de Haan (2007).
Localization and membrane topology of coronavirus nonstructural protein 4: involvement of the early secretory pathway in replication.
  J Virol, 81, 12323-12336.  
17450553 Q.S.Du, R.B.Huang, Y.T.Wei, C.H.Wang, and K.C.Chou (2007).
Peptide reagent design based on physical and chemical properties of amino acid residues.
  J Comput Chem, 28, 2043-2050.  
16928755 S.G.Sawicki, D.L.Sawicki, and S.G.Siddell (2007).
A contemporary view of coronavirus transcription.
  J Virol, 81, 20-29.  
16998715 S.Q.Wang, Q.S.Du, K.Zhao, A.X.Li, D.Q.Wei, and K.C.Chou (2007).
Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy.
  Amino Acids, 33, 129-135.  
17204484 T.E.Reddy, B.E.Shakhnovich, D.S.Roberts, S.J.Russek, and C.DeLisi (2007).
Positional clustering improves computational binding site detection and identifies novel cis-regulatory sites in mammalian GABAA receptor subunit genes.
  Nucleic Acids Res, 35, e20.  
17934078 V.C.Cheng, S.K.Lau, P.C.Woo, and K.Y.Yuen (2007).
Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection.
  Clin Microbiol Rev, 20, 660-694.  
  17671377 X.Tian, Y.Feng, T.Zhao, H.Peng, J.Yan, J.Qi, F.Jiang, K.Tian, and F.Gao (2007).
Molecular cloning, expression, purification and crystallographic analysis of PRRSV 3CL protease.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 720-722.  
16604207 A.Brik, C.Y.Wu, and C.H.Wong (2006).
Microtiter plate based chemistry and in situ screening: a useful approach for rapid inhibitor discovery.
  Org Biomol Chem, 4, 1446-1457.  
16503362 A.E.Gorbalenya, L.Enjuanes, J.Ziebuhr, and E.J.Snijder (2006).
Nidovirales: evolving the largest RNA virus genome.
  Virus Res, 117, 17-37.  
16641296 C.E.Zeitler, M.K.Estes, and B.V.Venkataram Prasad (2006).
X-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution.
  J Virol, 80, 5050-5058.
PDB codes: 2fyq 2fyr
16715412 D.Q.Wei, R.Zhang, Q.S.Du, W.N.Gao, Y.Li, H.Gao, S.Q.Wang, X.Zhang, A.X.Li, S.Sirois, and K.C.Chou (2006).
Anti-SARS drug screening by molecular docking.
  Amino Acids, 31, 73-80.  
16537610 D.van Aken, E.J.Snijder, and A.E.Gorbalenya (2006).
Mutagenesis analysis of the nsp4 main proteinase reveals determinants of arterivirus replicase polyprotein autoprocessing.
  J Virol, 80, 3428-3437.  
16597209 E.De Clercq (2006).
Potential antivirals and antiviral strategies against SARS coronavirus infections.
  Expert Rev Anti Infect Ther, 4, 291-302.  
16731931 E.J.Snijder, Y.van der Meer, J.Zevenhoven-Dobbe, J.J.Onderwater, J.van der Meulen, H.K.Koerten, and A.M.Mommaas (2006).
Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex.
  J Virol, 80, 5927-5940.  
16928748 F.Almazán, M.L.Dediego, C.Galán, D.Escors, E.Alvarez, J.Ortego, I.Sola, S.Zuñiga, S.Alonso, J.L.Moreno, A.Nogales, C.Capiscol, and L.Enjuanes (2006).
Construction of a severe acute respiratory syndrome coronavirus infectious cDNA clone and a replicon to study coronavirus RNA synthesis.
  J Virol, 80, 10900-10906.  
16987966 H.Schütze, R.Ulferts, B.Schelle, S.Bayer, H.Granzow, B.Hoffmann, T.C.Mettenleiter, and J.Ziebuhr (2006).
Characterization of White bream virus reveals a novel genetic cluster of nidoviruses.
  J Virol, 80, 11598-11609.  
16799548 I.L.Medintz, A.R.Clapp, F.M.Brunel, T.Tiefenbrunn, H.T.Uyeda, E.L.Chang, J.R.Deschamps, P.E.Dawson, and H.Mattoussi (2006).
Proteolytic activity monitored by fluorescence resonance energy transfer through quantum-dot-peptide conjugates.
  Nat Mater, 5, 581-589.  
17154528 J.Barrila, U.Bacha, and E.Freire (2006).
Long-range cooperative interactions modulate dimerization in SARS 3CLpro.
  Biochemistry, 45, 14908-14916.  
17085042 J.R.Mesters, J.Tan, and R.Hilgenfeld (2006).
Viral enzymes.
  Curr Opin Struct Biol, 16, 776-786.  
16478476 J.Shi, and J.Song (2006).
The catalysis of the SARS 3C-like protease is under extensive regulation by its extra domain.
  FEBS J, 273, 1035-1045.  
16581910 K.Ratia, K.S.Saikatendu, B.D.Santarsiero, N.Barretto, S.C.Baker, R.C.Stevens, and A.D.Mesecar (2006).
Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
  Proc Natl Acad Sci U S A, 103, 5717-5722.
PDB code: 2fe8
16600962 L.H.Chu, W.Y.Choy, S.N.Tsai, Z.Rao, and S.M.Ngai (2006).
Rapid peptide-based screening on the substrate specificity of severe acute respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
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16804033 M.D.Sørensen, B.Sørensen, R.Gonzalez-Dosal, C.J.Melchjorsen, J.Weibel, J.Wang, C.W.Jun, Y.Huanming, and P.Kristensen (2006).
Severe acute respiratory syndrome (SARS): development of diagnostics and antivirals.
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16895476 P.Hamill, D.Hudson, R.Y.Kao, P.Chow, M.Raj, H.Xu, M.J.Richer, and F.Jean (2006).
Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata.
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16688706 S.I.Al-Gharabli, S.T.Shah, S.Weik, M.F.Schmidt, J.R.Mesters, D.Kuhn, G.Klebe, R.Hilgenfeld, and J.Rademann (2006).
An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors.
  Chembiochem, 7, 1048-1055.  
  16582498 S.Ricagno, B.Coutard, S.Grisel, N.Brémond, K.Dalle, F.Tocque, V.Campanacci, J.Lichière, V.Lantez, C.Debarnot, C.Cambillau, B.Canard, and M.P.Egloff (2006).
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Binding site-based classification of coronaviral papain-like proteases.
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16188975 A.Putics, W.Filipowicz, J.Hall, A.E.Gorbalenya, and J.Ziebuhr (2005).
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15693056 B.Liu, and J.Zhou (2005).
SARS-CoV protease inhibitors design using virtual screening method from natural products libraries.
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  15833113 C.J.Stark, and C.D.Atreya (2005).
Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies.
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15937562 C.N.Chen, C.P.Lin, K.K.Huang, W.C.Chen, H.P.Hsieh, P.H.Liang, and J.T.Hsu (2005).
Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3'-digallate (TF3).
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15661082 D.A.Groneberg, R.Hilgenfeld, and P.Zabel (2005).
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15742319 D.N.Gosalia, C.M.Salisbury, D.J.Maly, J.A.Ellman, and S.L.Diamond (2005).
Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays.
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16271880 E.Garman (2005).
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16128623 H.Yang, W.Xie, X.Xue, K.Yang, J.Ma, W.Liang, Q.Zhao, Z.Zhou, D.Pei, J.Ziebuhr, R.Hilgenfeld, K.Y.Yuen, L.Wong, G.Gao, S.Chen, Z.Chen, D.Ma, M.Bartlam, and Z.Rao (2005).
Design of wide-spectrum inhibitors targeting coronavirus main proteases.
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PDB codes: 1wof 2amd 2amp 2amq 2d2d
15999208 J.H.Lu, D.M.Zhang, G.L.Wang, Z.M.Guo, J.Li, B.Y.Tan, L.P.Ou-Yang, W.H.Ling, X.B.Yu, and N.S.Zhong (2005).
Sequence analysis and structural prediction of the severe acute respiratory syndrome coronavirus nsp5.
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16227288 K.Nakamura, Y.Someya, T.Kumasaka, G.Ueno, M.Yamamoto, T.Sato, N.Takeda, T.Miyamura, and N.Tanaka (2005).
A norovirus protease structure provides insights into active and substrate binding site integrity.
  J Virol, 79, 13685-13693.
PDB code: 1wqs
15890949 L.Chen, C.Gui, X.Luo, Q.Yang, S.Günther, E.Scandella, C.Drosten, D.Bai, X.He, B.Ludewig, J.Chen, H.Luo, Y.Yang, Y.Yang, J.Zou, V.Thiel, K.Chen, J.Shen, X.Shen, and H.Jiang (2005).
Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.
  J Virol, 79, 7095-7103.  
15693054 N.S.Yang, J.H.Wang, K.F.Lin, C.Y.Wang, S.A.Kim, Y.L.Yang, M.H.Jong, T.Y.Kuo, S.S.Lai, R.H.Cheng, M.T.Chan, and S.M.Liang (2005).
Comparative studies of the capsid precursor polypeptide P1 and the capsid protein VP1 cDNA vectors for DNA vaccination against foot-and-mouth disease virus.
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15659121 S.Chen, L.L.Chen, H.B.Luo, T.Sun, J.Chen, F.Ye, J.H.Cai, J.K.Shen, X.Shen, and H.L.Jiang (2005).
Enzymatic activity characterization of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer technique.
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16341254 S.G.Sawicki, D.L.Sawicki, D.Younker, Y.Meyer, V.Thiel, H.Stokes, and S.G.Siddell (2005).
Functional and genetic analysis of coronavirus replicase-transcriptase proteins.
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16287687 S.S.Wong, and K.Y.Yuen (2005).
The severe acute respiratory syndrome (SARS).
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16331324 Y.F.Shan, and G.J.Xu (2005).
Study on substrate specificity at subsites for severe acute respiratory syndrome coronavirus 3CL protease.
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15797903 Z.R.Yang (2005).
Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection.
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15279849 A.Hillisch, L.F.Pineda, and R.Hilgenfeld (2004).
Utility of homology models in the drug discovery process.
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15220404 B.C.Fielding, Y.J.Tan, S.Shuo, T.H.Tan, E.E.Ooi, S.G.Lim, W.Hong, and P.Y.Goh (2004).
Characterization of a unique group-specific protein (U122) of the severe acute respiratory syndrome coronavirus.
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15564471 B.H.Harcourt, D.Jukneliene, A.Kanjanahaluethai, J.Bechill, K.M.Severson, C.M.Smith, P.A.Rota, and S.C.Baker (2004).
Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity.
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15226499 C.Y.Wu, J.T.Jan, S.H.Ma, C.J.Kuo, H.F.Juan, Y.S.Cheng, H.H.Hsu, H.C.Huang, D.Wu, A.Brik, F.S.Liang, R.S.Liu, J.M.Fang, S.T.Chen, P.H.Liang, and C.H.Wong (2004).
Small molecules targeting severe acute respiratory syndrome human coronavirus.
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15264983 D.S.Hui, and G.W.Wong (2004).
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15372081 E.De Clercq (2004).
Antivirals and antiviral strategies.
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14962394 G.Sutton, E.Fry, L.Carter, S.Sainsbury, T.Walter, J.Nettleship, N.Berrow, R.Owens, R.Gilbert, A.Davidson, S.Siddell, L.L.Poon, J.Diprose, D.Alderton, M.Walsh, J.M.Grimes, and D.I.Stuart (2004).
The nsp9 replicase protein of SARS-coronavirus, structure and functional insights.
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PDB code: 1uw7
15489171 J.E.Blanchard, N.H.Elowe, C.Huitema, P.D.Fortin, J.D.Cechetto, L.D.Eltis, and E.D.Brown (2004).
High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.
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Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry.
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15165176 J.Kopp, and T.Schwede (2004).
Automated protein structure homology modeling: a progress report.
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Fluorescent probes for proteolysis: tools for drug discovery.
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15280490 J.R.St-Jean, H.Jacomy, M.Desforges, A.Vabret, F.Freymuth, and P.J.Talbot (2004).
Human respiratory coronavirus OC43: genetic stability and neuroinvasion.
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Severe acute respiratory syndrome.
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Mosaic evolution of the severe acute respiratory syndrome coronavirus.
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Molecular biology of severe acute respiratory syndrome coronavirus.
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15220459 K.A.Ivanov, and J.Ziebuhr (2004).
Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities.
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15304651 K.A.Ivanov, T.Hertzig, M.Rozanov, S.Bayer, V.Thiel, A.E.Gorbalenya, and J.Ziebuhr (2004).
Major genetic marker of nidoviruses encodes a replicative endoribonuclease.
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15140959 K.A.Ivanov, V.Thiel, J.C.Dobbe, Y.van der Meer, E.J.Snijder, and J.Ziebuhr (2004).
Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase.
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15507608 K.Bhardwaj, L.Guarino, and C.C.Kao (2004).
The severe acute respiratory syndrome coronavirus Nsp15 protein is an endoribonuclease that prefers manganese as a cofactor.
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15180906 L.Kiemer, O.Lund, S.Brunak, and N.Blom (2004).
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The aetiology, origins, and diagnosis of severe acute respiratory syndrome.
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15071371 M.J.Brooks, J.J.Sasadeusz, and G.A.Tannock (2004).
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15564515 M.Parera, B.Clotet, and M.A.Martinez (2004).
Genetic screen for monitoring severe acute respiratory syndrome coronavirus 3C-like protease.
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15133227 M.Takeda-Shitaka, H.Nojima, D.Takaya, K.Kanou, M.Iwadate, and H.Umeyama (2004).
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Novel and re-emerging respiratory infections.
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15241071 S.M.Poutanen, and D.E.Low (2004).
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15449910 T.Mizutani (2004).
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  Uirusu, 54, 97.  
15060002 X.S.Puente, and C.López-Otín (2004).
A genomic analysis of rat proteases and protease inhibitors.
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15690493 Y.P.Pang (2004).
Three-dimensional model of a substrate-bound SARS chymotrypsin-like cysteine proteinase predicted by multiple molecular dynamics simulations: catalytic efficiency regulated by substrate binding.
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PDB codes: 1p76 2aj5
14624107 A.Davidson, and S.Siddell (2003).
Potential for antiviral treatment of severe acute respiratory syndrome.
  Curr Opin Infect Dis, 16, 565-571.  
14609438 A.Wlodawer, S.R.Durell, M.Li, H.Oyama, K.Oda, and B.M.Dunn (2003).
A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases.
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PDB code: 1r60
14569023 B.Yount, K.M.Curtis, E.A.Fritz, L.E.Hensley, P.B.Jahrling, E.Prentice, M.R.Denison, T.W.Geisbert, and R.S.Baric (2003).
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Coronavirus in severe acute respiratory syndrome (SARS).
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14585926 H.Yang, M.Yang, Y.Ding, Y.Liu, Z.Lou, Z.Zhou, L.Sun, L.Mo, S.Ye, H.Pang, G.F.Gao, K.Anand, M.Bartlam, R.Hilgenfeld, and Z.Rao (2003).
The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor.
  Proc Natl Acad Sci U S A, 100, 13190-13195.
PDB codes: 1uj1 1uk2 1uk3 1uk4
15035025 K.Stadler, V.Masignani, M.Eickmann, S.Becker, S.Abrignani, H.D.Klenk, and R.Rappuoli (2003).
SARS--beginning to understand a new virus.
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14605542 S.Manocha, K.R.Walley, and J.A.Russell (2003).
Severe acute respiratory distress syndrome (SARS): a critical care perspective.
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12925794 V.Campanacci, M.P.Egloff, S.Longhi, F.Ferron, C.Rancurel, A.Salomoni, C.Durousseau, F.Tocque, N.Brémond, J.C.Dobbe, E.J.Snijder, B.Canard, and C.Cambillau (2003).
Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein.
  Acta Crystallogr D Biol Crystallogr, 59, 1628-1631.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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