PDBsum entry 1iec

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protein Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
207 a.a. *
219 a.a. *
Waters ×144
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the catalytic site mutant (h157a) of th cytomegalovirus protease
Structure: Capsid protein p40: assemblin protease. Chain: a, b. Fragment: residues 1-256. Synonym: hcmv protease. Engineered: yes. Mutation: yes
Source: Human herpesvirus 5. Organism_taxid: 10360. Strain: ad169. Gene: ul80. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.226     R-free:   0.269
Authors: R.Khayat,R.Batra,M.J.Massariol,L.Lagace,L.Tong
Key ref:
R.Khayat et al. (2001). Investigating the role of histidine 157 in the catalytic activity of human cytomegalovirus protease. Biochemistry, 40, 6344-6351. PubMed id: 11371196 DOI: 10.1021/bi010158b
09-Apr-01     Release date:   06-Jun-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P16753  (PPR_HCMVA) -  Capsid scaffolding protein
708 a.a.
207 a.a.*
Protein chain
Pfam   ArchSchema ?
P16753  (PPR_HCMVA) -  Capsid scaffolding protein
708 a.a.
219 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Assemblin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     serine-type endopeptidase activity     1 term  


DOI no: 10.1021/bi010158b Biochemistry 40:6344-6351 (2001)
PubMed id: 11371196  
Investigating the role of histidine 157 in the catalytic activity of human cytomegalovirus protease.
R.Khayat, R.Batra, M.J.Massariol, L.Lagacé, L.Tong.
Herpesvirus proteases belong to a new class of serine proteases and contain a novel Ser-His-His catalytic triad, while classical serine proteases have an acidic residue as the third member. To gain a better understanding of the molecular basis for the functional role of the third-member His residue, we have carried out structural and biochemical investigations of human cytomegalovirus (HCMV) protease that bears mutations of the His157 third member. Kinetic studies showed that all the mutants have reduced catalytic activity. Structural studies revealed that a solvent molecule is hydrogen-bonded to the His63 second member and Ser134 in the H157A mutant, partly rescuing the activity of this mutant. This is confirmed by our kinetic and structural observations on the S134A/H157A double mutant, which showed further reductions in the catalytic activity. The structure of the H157A mutant is also in complex with the PMSF inhibitor. The H157E mutant has the best catalytic activity among the mutants; its structure, however, showed conformational readjustments of the His63 and Ser132 residues. The Ser132-His63 diad of HCMV protease has similar activity as the diads in classical serine proteases, whereas the contribution of the His157 third member to the catalysis is much smaller. Finally, structural comparisons revealed the presence of two conserved structural water molecules at the bottom of the S(1) pocket, suggesting a possible new direction for the design of HCMV protease inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19213731 C.Y.Chou, L.P.Yu, and L.Tong (2009).
Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism.
  J Biol Chem, 284, 11690-11697.
PDB codes: 3g8c 3g8d
19217401 Q.Xu, S.Sudek, D.McMullan, M.D.Miller, B.Geierstanger, D.H.Jones, S.S.Krishna, G.Spraggon, B.Bursalay, P.Abdubek, C.Acosta, E.Ambing, T.Astakhova, H.L.Axelrod, D.Carlton, J.Caruthers, H.J.Chiu, T.Clayton, M.C.Deller, L.Duan, Y.Elias, M.A.Elsliger, J.Feuerhelm, S.K.Grzechnik, J.Hale, G.Won Han, J.Haugen, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, P.Kozbial, A.Kumar, D.Marciano, A.T.Morse, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, R.Reyes, C.L.Rife, C.V.Trout, H.van den Bedem, D.Weekes, A.White, G.Wolf, C.Zubieta, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2009).
Structural basis of murein peptide specificity of a gamma-D-glutamyl-l-diamino acid endopeptidase.
  Structure, 17, 303-313.
PDB codes: 2evr 2fg0 2hbw
18824507 O.D.Ekici, M.Paetzel, and R.E.Dalbey (2008).
Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration.
  Protein Sci, 17, 2023-2037.  
17870089 A.Lazic, D.H.Goetz, A.M.Nomura, A.B.Marnett, and C.S.Craik (2007).
Substrate modulation of enzyme activity in the herpesvirus protease family.
  J Mol Biol, 373, 913-923.
PDB code: 2pbk
15118083 A.B.Marnett, A.M.Nomura, N.Shimba, P.R.Ortiz de Montellano, and C.S.Craik (2004).
Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor.
  Proc Natl Acad Sci U S A, 101, 6870-6875.  
15273316 H.Cheng, N.Shen, J.Pei, and N.V.Grishin (2004).
Double-stranded DNA bacteriophage prohead protease is homologous to herpesvirus protease.
  Protein Sci, 13, 2260-2269.  
15205439 J.Liu, and A.Mushegian (2004).
Displacements of prohead protease genes in the late operons of double-stranded-DNA bacteriophages.
  J Bacteriol, 186, 4369-4375.  
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.