PDBsum entry 2pmq

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protein metals Protein-protein interface(s) links
Isomerase PDB id
Protein chains
367 a.a. *
_MG ×5
Waters ×687
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of a mandelate racemase/muconate lactonizi from roseovarius sp. Htcc2601
Structure: Mandelate racemase/muconate lactonizing enzyme. Chain: a, b. Engineered: yes
Source: Roseovarius sp.. Organism_taxid: 314265. Strain: htcc2601. Gene: r2601_01638. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.72Å     R-factor:   0.167     R-free:   0.191
Authors: J.B.Bonanno,M.Rutter,K.T.Bain,C.Lau,V.Sridhar,D.Smith,S.Wass J.M.Sauder,S.K.Burley,S.C.Almo,New York Sgx Research Center Structural Genomics (Nysgxrc)
Key ref: S.Zhao et al. (2013). Discovery of new enzymes and metabolic pathways by using structure and genome context. Nature, 502, 698-702. PubMed id: 24056934 DOI: 10.1038/nature12576
23-Apr-07     Release date:   08-May-07    
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Protein chains
Pfam   ArchSchema ?
Q0FPQ4  (Q0FPQ4_9RHOB) -  4-hydroxyproline betaine 2-epimerase
367 a.a.
367 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1038/nature12576 Nature 502:698-702 (2013)
PubMed id: 24056934  
Discovery of new enzymes and metabolic pathways by using structure and genome context.
S.Zhao, R.Kumar, A.Sakai, M.W.Vetting, B.M.Wood, S.Brown, J.B.Bonanno, B.S.Hillerich, R.D.Seidel, P.C.Babbitt, S.C.Almo, J.V.Sweedler, J.A.Gerlt, J.E.Cronan, M.P.Jacobson.
Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.