PDBsum entry 2x30

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Isomerase PDB id
Protein chain
233 a.a. *
SO4 ×2
Waters ×126
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of the r139n mutant of a bifunctional enzyme pria
Structure: Phosphoribosyl isomerase a. Chain: a. Synonym: 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino) methylideneamino] imidazole-4-carboxamide isomerase, phosphoribosylformimino-5-aminoimidazole carboxamide ribot isomerase, n-(5'-phosphoribosyl)anthranilate isomerase, pr engineered: yes. Mutation: yes
Source: Streptomyces coelicolor. Organism_taxid: 1902. Strain: sco2050. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.95Å     R-factor:   0.218     R-free:   0.272
Authors: L.Noda-Garcia,A.R.Camacho-Zarco,K.Verdel-Aranda,H.Wright,X.S V.Fulop,F.Barona-Gomez
Key ref: L.Noda-García et al. (2010). Identification and analysis of residues contained on beta --> alpha loops of the dual-substrate (beta alpha)8 phosphoribosyl isomerase A specific for its phosphoribosyl anthranilate isomerase activity. Protein Sci, 19, 535-543. PubMed id: 20066665
20-Jan-10     Release date:   02-Feb-10    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P16250  (HIS4_STRCO) -  Phosphoribosyl isomerase A
240 a.a.
233 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: E.C.  - 1-(5-phosphoribosyl)-5-
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Histidine Biosynthesis (early stages)
      Reaction: 1-(5-phospho-beta-D-ribosyl)-5-((5-phospho-beta-D- ribosylamino)methylideneamino)imidazole-4-carboxamide = 5-((5-phospho-1- deoxy-D-ribulos-1-ylamino)methylideneamino)-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide
   Enzyme class 3: E.C.  - Phosphoribosylanthranilate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
= 1-(2-carboxyphenylamino)-1- deoxy-D-ribulose 5-phosphate
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  


    Added reference    
Protein Sci 19:535-543 (2010)
PubMed id: 20066665  
Identification and analysis of residues contained on beta --> alpha loops of the dual-substrate (beta alpha)8 phosphoribosyl isomerase A specific for its phosphoribosyl anthranilate isomerase activity.
L.Noda-García, A.R.Camacho-Zarco, K.Verdel-Aranda, H.Wright, X.Soberón, V.Fülöp, F.Barona-Gómez.
A good model to experimentally explore evolutionary hypothesis related to enzyme function is the ancient-like dual-substrate (beta alpha)(8) phosphoribosyl isomerase A (PriA), which takes part in both histidine and tryptophan biosynthesis in Streptomyces coelicolor and related organisms. In this study, we determined the Michaelis-Menten enzyme kinetics for both isomerase activities in wild-type PriA from S. coelicolor and in selected single-residue monofunctional mutants, identified after Escherichia coli in vivo complementation experiments. Structural and functional analyses of a hitherto unnoticed residue contained on the functionally important beta --> alpha loop 5, namely, Arg(139), which was postulated on structural grounds to be important for the dual-substrate specificity of PriA, is presented for the first time. Indeed, enzyme kinetics analyses done on the mutant variants PriA_Ser(81)Thr and PriA_Arg(139)Asn showed that these residues, which are contained on beta --> alpha loops and in close proximity to the N-terminal phosphate-binding site, are essential solely for the phosphoribosyl anthranilate isomerase activity of PriA. Moreover, analysis of the X-ray crystallographic structure of PriA_Arg(139)Asn elucidated at 1.95 A herein strongly implicates the occurrence of conformational changes in this beta --> alpha loop as a major structural feature related to the evolution of the dual-substrate specificity of PriA. It is suggested that PriA has evolved by tuning a fine energetic balance that allows the sufficient degree of structural flexibility needed for accommodating two topologically dissimilar substrates--within a bifunctional and thus highly constrained active site--without compromising its structural stability.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21321225 A.V.Due, J.Kuper, A.Geerlof, J.P.Kries, and M.Wilmanns (2011).
Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.
  Proc Natl Acad Sci U S A, 108, 3554-3559.
PDB codes: 2y85 2y88 2y89
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.