PDBsum entry 4x9s

Isomerase

PDB id: 4x9s

Contents

Protein chain

241 a.a.

Ligands

SO4 ×5

Waters ×229

PDB id:

4x9s

Name:

Isomerase

Title:

Crystal structure of hisap from streptomyces sp. Mg1

Structure:

Phosphoribosyl isomerase a. Chain: a. Synonym: 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino) methylideneamino] imidazole-4-carboxamide isomerase,n-(5'- phosphoribosyl)anthranilate isomerase,phosphoribosylformimino-5- aminoimidazole carboxamide ribotide isomerase. Engineered: yes

Source:

Streptomyces sp. Mg1. Organism_taxid: 465541. Gene: pria, hisa, ssag_02214. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.156 R-free: 0.190

Authors:

K.Michalska,E.A.Verduzco-Castro,M.Endres,F.Barona-Gomez,A.Joachimiak, Midwest Center For Structural Genomics (Mcsg)

Key ref:

E.A.Verduzco-Castro et al. (2016). Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop. Biochem J, 473, 1141-1152. PubMed id: 26929404 DOI: 10.1042/BJ20151271

Date:

11-Dec-14 Release date: 24-Dec-14

Protein chain

B4V386  (B4V386_9ACTN) -  Phosphoribosyl isomerase A from Streptomyces sp. Mg1

Seq: 243 a.a.

Struc: 241 a.a.

Enzyme reactions

• Enzyme class 2: E.C.5.3.1.16 - 1-(5-phosphoribosyl)-5-
• Pathway: 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-ylimino)methylamino]-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide
• Enzyme class 3: E.C.5.3.1.24 - phosphoribosylanthranilate isomerase.

Pathway:

• Reaction: N-(5-phospho-beta-D-ribosyl)anthranilate = 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

Added reference

DOI no: 10.1042/BJ20151271

Biochem J 473:1141-1152 (2016)

PubMed id: 26929404

Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop.

E.A.Verduzco-Castro, K.Michalska, M.Endres, A.L.Juárez-Vazquez, L.Noda-García, C.Chang, C.S.Henry, G.Babnigg, A.Joachimiak, F.Barona-Gómez.

ABSTRACT

We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1 We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1 Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Thus, the PriA homologues that co-occur with TrpF-3 represent a novel enzyme family, termed PriB, which evolved in response to PRA isomerase activity. The characterization of co-occurring enzymes provides insights into the influence of functional redundancy on the evolution of enzyme function, which could be useful for enzyme functional annotation.