PDBsum entry 1sjb

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protein ligands metals Protein-protein interface(s) links
Lyase, isomerase PDB id
Jmol PyMol
Protein chains
367 a.a. *
OSB ×4
_MG ×4
Waters ×774
* Residue conservation analysis
PDB id:
Name: Lyase, isomerase
Title: X-ray structure of o-succinylbenzoate synthase complexed with o-succinylbenzoic acid
Structure: N-acylamino acid racemase. Chain: a, b, c, d. Synonym: o-succinylbenzoate synthase. Engineered: yes
Source: Amycolatopsis sp.. Organism_taxid: 37632. Gene: aaar. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Octamer (from PDB file)
2.20Å     R-factor:   0.209     R-free:   0.272
Authors: J.B.Thoden,E.A.Taylor-Ringia,J.B.Garrett,J.A.Gerlt, H.M.Holden,I.Rayment
Key ref:
J.B.Thoden et al. (2004). Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis. Biochemistry, 43, 5716-5727. PubMed id: 15134446 DOI: 10.1021/bi0497897
03-Mar-04     Release date:   01-Jun-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q44244  (Q44244_9PSEU) -  o-succinylbenzoate synthase
368 a.a.
367 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     menaquinone biosynthetic process   1 term 
  Biochemical function     lyase activity     4 terms  


DOI no: 10.1021/bi0497897 Biochemistry 43:5716-5727 (2004)
PubMed id: 15134446  
Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis.
J.B.Thoden, E.A.Taylor Ringia, J.B.Garrett, J.A.Gerlt, H.M.Holden, I.Rayment.
Divergent evolution of enzyme function is commonly explained by a gene duplication event followed by mutational changes that allow the protein encoded by the copy to acquire a new function. An alternate hypothesis is that this process is facilitated when the progenitor enzyme acquires a second function while maintaining the original activity. This phenomenon has been suggested to occur in the o-succinylbenzoate synthase (OSBS) from a species of Amycolatopsis that catalyzes not only the physiological syn-dehydration reaction of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate but also an accidental racemization of N-acylamino acids [Palmer, D. R., Garrett, J. B., Sharma, V., Meganathan, R., Babbitt, P. C., and Gerlt, J. A. (1999) Biochemistry 38, 4252-4258]. To understand the molecular basis of this promiscuity, three-dimensional structures of liganded complexes of this enzyme have been determined, including the product of the OSBS reaction and three N-acylamino acid substrates for the N-acylamino acid racemase (NAAAR) reaction, N-acetylmethionine, N-succinylmethionine, and N-succinylphenylglycine, to 2.2, 2.3, 2.1, and 1.9 A resolution, respectively. These structures show how the active-site cavity can accommodate both the hydrophobic substrate for the OSBS reaction and the substrates for the accidental NAAAR reaction. As expected, the N-acylamino acid is sandwiched between lysines 163 and 263, which function as the catalytic bases for the abstraction of the alpha-proton in the (R)- and (S)-racemization reactions, respectively [Taylor Ringia, E. A., Garrett, J. B, Thoden, J. B., Holden, H. M., Rayment, I., and Gerlt, J. A. (2004) Biochemistry 42, 224-229]. Importantly, the protein forms specific favorable interactions with the hydrophobic amino acid side chain, alpha-carbon, carboxylate, and the polar components of the N-acyl linkage. Accommodation of the components of the N-acyl linkage appears to be the reason that this enzyme is capable of a racemization reaction on these substrates, whereas the orthologous OSBS from Escherichia coli lacks this functionality.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.  
18214979 M.Hayashida, S.H.Kim, K.Takeda, T.Hisano, and K.Miki (2008).
Crystal structure of N-acylamino acid racemase from Thermus thermophilus HB8.
  Proteins, 71, 519-523.
PDB code: 2zc8
17379338 K.Hult, and P.Berglund (2007).
Enzyme promiscuity: mechanism and applications.
  Trends Biotechnol, 25, 231-238.  
17561509 L.Hou, M.T.Honaker, L.M.Shireman, L.M.Balogh, A.G.Roberts, K.C.Ng, A.Nath, and W.M.Atkins (2007).
Functional promiscuity correlates with conformational heterogeneity in A-class glutathione S-transferases.
  J Biol Chem, 282, 23264-23274.  
17603539 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, and J.A.Gerlt (2007).
Prediction and assignment of function for a divergent N-succinyl amino acid racemase.
  Nat Chem Biol, 3, 486-491.
PDB codes: 2p88 2p8b 2p8c
19404462 R.Wroe, H.S.Chan, and E.Bornberg-Bauer (2007).
A structural model of latent evolutionary potentials underlying neutral networks in proteins.
  HFSP J, 1, 79-87.  
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