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PDBsum entry 2p8c
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protein ligands metals links
Lyase PDB id
2p8c

 

 

 

 

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Contents
Protein chain
369 a.a. *
Ligands
SUG
Metals
_MG
Waters ×165
* Residue conservation analysis
PDB id:
2p8c
Name: Lyase
Title: Crystal structure of n-succinyl arg/lys racemase from bacillus cereus atcc 14579 complexed with n-succinyl arg.
Structure: Mandelate racemase/muconate lactonizing enzyme family protein. Chain: a. Engineered: yes
Source: Bacillus cereus atcc 14579. Organism_taxid: 226900. Strain: dsm 31. Gene: bc_0371. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.00Å     R-factor:   0.180     R-free:   0.199
Authors: A.A.Fedorov,L.Song,E.V.Fedorov,J.A.Gerlt,S.C.Almo
Key ref:
L.Song et al. (2007). Prediction and assignment of function for a divergent N-succinyl amino acid racemase. Nat Chem Biol, 3, 486-491. PubMed id: 17603539 DOI: 10.1038/nchembio.2007.11
Date:
22-Mar-07     Release date:   03-Jul-07    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q81IL5  (NSAR_BACCR) -  N-succinyl-L-Arg/Lys racemase from Bacillus cereus (strain ATCC 14579 / DSM 31 / CCUG 7414 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NCTC 2599 / NRRL B-3711)
Seq:
Struc: 		369 a.a.
369 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.1.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1038/nchembio.2007.11 Nat Chem Biol 3:486-491 (2007)
PubMed id: 17603539  
 
 
Prediction and assignment of function for a divergent N-succinyl amino acid racemase.
L.Song, C.Kalyanaraman, A.A.Fedorov, E.V.Fedorov, M.E.Glasner, S.Brown, H.J.Imker, P.C.Babbitt, S.C.Almo, M.P.Jacobson, J.A.Gerlt.
 
  ABSTRACT  
 
The protein databases contain many proteins with unknown function. A computational approach for predicting ligand specificity that requires only the sequence of the unknown protein would be valuable for directing experiment-based assignment of function. We focused on a family of unknown proteins in the mechanistically diverse enolase superfamily and used two approaches to assign function: (i) enzymatic assays using libraries of potential substrates, and (ii) in silico docking of the same libraries using a homology model based on the most similar (35% sequence identity) characterized protein. The results matched closely; an experimentally determined structure confirmed the predicted structure of the substrate-liganded complex. We assigned the N-succinyl arginine/lysine racemase function to the family, correcting the annotation (L-Ala-D/L-Glu epimerase) based on the function of the most similar characterized homolog. These studies establish that ligand docking to a homology model can facilitate functional assignment of unknown proteins by restricting the identities of the possible substrates that must be experimentally tested.
 
  Selected figure(s)  
 
Figure 2.
(a) AEE from B. subtilis with the L-Ala-L-Glu ligand as determined by X-ray crystallography. (b) BC0371 with the N-succinyl-L-arginine ligand as predicted by homology modeling and docking. Catalytic residues are shown in tube representation; ligands and critical binding site residues are shown in ball-and-stick representation. 		Figure 3.
The homology-modeled active site is shown in cyan, and the experimentally determined active site is shown in yellow. The residues that determine substrate specificity are labeled.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Chem Biol (2007, 3, 486-491) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20415432 C.Kalyanaraman, and M.P.Jacobson (2010).
Studying enzyme-substrate specificity in silico: a case study of the Escherichia coli glycolysis pathway.
  Biochemistry, 49, 4003-4005.  
21079586 M.Bucci, C.Goodman, and T.L.Sheppard (2010).
A decade of chemical biology.
  Nat Chem Biol, 6, 847-854.  
20810277 M.Chruszcz, M.Domagalski, T.Osinski, A.Wlodawer, and W.Minor (2010).
Unmet challenges of structural genomics.
  Curr Opin Struct Biol, 20, 587-597.  
20078397 V.Vacic, L.M.Iakoucheva, S.Lonardi, and P.Radivojac (2010).
Graphlet kernels for prediction of functional residues in protein structures.
  J Comput Biol, 17, 55-72.  
19220063 A.Sakai, A.A.Fedorov, E.V.Fedorov, A.M.Schnoes, M.E.Glasner, S.Brown, M.E.Rutter, K.Bain, S.Chang, T.Gheyi, J.M.Sauder, S.K.Burley, P.C.Babbitt, S.C.Almo, and J.A.Gerlt (2009).
Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymes.
  Biochemistry, 48, 1445-1453.
PDB codes: 3ct2 3dg3 3dg6 3dg7 3dgb 3fj4
19398323 B.H.Dessailly, O.C.Redfern, A.Cuff, and C.A.Orengo (2009).
Exploiting structural classifications for function prediction: towards a domain grammar for protein function.
  Curr Opin Struct Biol, 19, 349-356.  
19422931 C.N.Cavasotto, and S.S.Phatak (2009).
Homology modeling in drug discovery: current trends and applications.
  Drug Discov Today, 14, 676-683.  
19845314 H.Fan, J.J.Irwin, B.M.Webb, G.Klebe, B.K.Shoichet, and A.Sali (2009).
Molecular docking screens using comparative models of proteins.
  J Chem Inf Model, 49, 2512-2527.  
19190775 H.J.Atkinson, J.H.Morris, T.E.Ferrin, and P.C.Babbitt (2009).
Using sequence similarity networks for visualization of relationships across diverse protein superfamilies.
  PLoS ONE, 4, e4345.  
19883118 J.F.Rakus, C.Kalyanaraman, A.A.Fedorov, E.V.Fedorov, F.P.Mills-Groninger, R.Toro, J.Bonanno, K.Bain, J.M.Sauder, S.K.Burley, S.C.Almo, M.P.Jacobson, and J.A.Gerlt (2009).
Computation-facilitated assignment of the function in the enolase superfamily: a regiochemically distinct galactarate dehydratase from Oceanobacillus iheyensis .
  Biochemistry, 48, 11546-11558.
PDB codes: 2oqy 3es7 3es8 3fyy 3hpf
19493341 P.B.Juhl, P.Trodler, S.Tyagi, and J.Pleiss (2009).
Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking.
  BMC Struct Biol, 9, 39.  
  20948600 S.D.Copley (2009).
Prediction of function in protein superfamilies.
  F1000 Biol Rep, 1, 0.  
19217386 T.Schwede, A.Sali, B.Honig, M.Levitt, H.M.Berman, D.Jones, S.E.Brenner, S.K.Burley, R.Das, N.V.Dokholyan, R.L.Dunbrack, K.Fidelis, A.Fiser, A.Godzik, Y.J.Huang, C.Humblet, M.P.Jacobson, A.Joachimiak, S.R.Krystek, T.Kortemme, A.Kryshtafovych, G.T.Montelione, J.Moult, D.Murray, R.Sanchez, T.R.Sosnick, D.M.Standley, T.Stouch, S.Vajda, M.Vasquez, J.D.Westbrook, and I.A.Wilson (2009).
Outcome of a workshop on applications of protein models in biomedical research.
  Structure, 17, 151-159.  
19219566 U.Pieper, R.Chiang, J.J.Seffernick, S.D.Brown, M.E.Glasner, L.Kelly, N.Eswar, J.M.Sauder, J.B.Bonanno, S.Swaminathan, S.K.Burley, X.Zheng, M.R.Chance, S.C.Almo, J.A.Gerlt, F.M.Raushel, M.P.Jacobson, P.C.Babbitt, and A.Sali (2009).
Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies.
  J Struct Funct Genomics, 10, 107-125.  
18280498 A.P.Graves, D.M.Shivakumar, S.E.Boyce, M.P.Jacobson, D.A.Case, and B.K.Shoichet (2008).
Rescoring docking hit lists for model cavity sites: predictions and experimental testing.
  J Mol Biol, 377, 914-934.
PDB codes: 2ray 2raz 2rb0 2rb1 2rb2 2rbn 2rbo 2rbp 2rbq 2rbr 2rbs 2rbt 2rbu 2rbv 2rbw 2rbx 2rby 2rbz 2rc0 2rc1 2rc2
19000819 C.Kalyanaraman, H.J.Imker, A.A.Fedorov, E.V.Fedorov, M.E.Glasner, P.C.Babbitt, S.C.Almo, J.A.Gerlt, and M.P.Jacobson (2008).
Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening.
  Structure, 16, 1668-1677.
PDB codes: 3deq 3der 3des 3dfy
18620864 D.Chen, M.Misra, L.Sower, J.W.Peterson, G.E.Kellogg, and C.H.Schein (2008).
Novel inhibitors of anthrax edema factor.
  Bioorg Med Chem, 16, 7225-7233.  
19000810 D.Dunaway-Mariano (2008).
Enzyme function discovery.
  Structure, 16, 1599-1600.  
18826254 H.J.Imker, J.Singh, B.P.Warlick, F.R.Tabita, and J.A.Gerlt (2008).
Mechanistic diversity in the RuBisCO superfamily: a novel isomerization reaction catalyzed by the RuBisCO-like protein from Rhodospirillum rubrum.
  Biochemistry, 47, 11171-11173.  
18312862 J.Bajorath (2008).
Computational analysis of ligand relationships within target families.
  Curr Opin Chem Biol, 12, 352-358.  
18754693 J.F.Rakus, A.A.Fedorov, E.V.Fedorov, M.E.Glasner, B.K.Hubbard, J.D.Delli, P.C.Babbitt, S.C.Almo, and J.A.Gerlt (2008).
Evolution of enzymatic activities in the enolase superfamily: L-rhamnonate dehydratase.
  Biochemistry, 47, 9944-9954.
PDB codes: 2i5q 3box 3cxo
18670595 R.A.Chiang, A.Sali, and P.C.Babbitt (2008).
Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies.
  PLoS Comput Biol, 4, e1000142.  
17637773 K.N.Allen (2007).
Form finds function.
  Nat Chem Biol, 3, 452-453.  
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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