4AXK

CRYSTAL STRUCTURE OF subHisA from the thermophile Corynebacterium efficiens

Summary for 4AXK

• Entry DOI: 10.2210/pdb4axk/pdb
• Descriptor: 1-(5-PHOSPHORIBOSYL)-5-((5'-PHOSPHORIBOSYLAMINO) METHYLIDENEAMINO)IMIDAZOLE-4-CARBOXAMIDE ISOMERASE, GLYCEROL (3 entities in total)
• Functional Keywords: isomerase, (beta-alpha)8-barrel, metabolism, evolution of substrate specificity, histidine biosynthesis
• Biological source: CORYNEBACTERIUM EFFICIENS
• Cellular location: Cytoplasm (By similarity): C8NPV3
• Total number of polymer chains: 2
• Total formula weight: 54256.72

Authors

Noda-Garcia, L.,Camacho-Zarco, A.R.,Medina-Ruiz, S.,Verduzco-Castro, E.A.,Gaytan, P.,Carrillo-Tripp, M.,Fulop, V.,Barona-Gomez, F. (deposition date: 2012-06-13, release date: 2013-06-26, Last modification date: 2023-12-20)

Primary citation

Noda-Garcia, L.,Camacho-Zarco, A.R.,Medina-Ruiz, S.,Gaytan, P.,Carrillo-Tripp, M.,Fulop, V.,Barona-Gomez, F.
Evolution of Substrate Specificity in a Recipient'S Enzyme Following Horizontal Gene Transfer.
Mol.Biol.Evol., 30:2024-, 2013

PubMed Abstract: Despite the prominent role of horizontal gene transfer (HGT) in shaping bacterial metabolism, little is known about the impact of HGT on the evolution of enzyme function. Specifically, what is the influence of a recently acquired gene on the function of an existing gene? For example, certain members of the genus Corynebacterium have horizontally acquired a whole l-tryptophan biosynthetic operon, whereas in certain closely related actinobacteria, for example, Mycobacterium, the trpF gene is missing. In Mycobacterium, the function of the trpF gene is performed by a dual-substrate (βα)8 phosphoribosyl isomerase (priA gene) also involved in l-histidine (hisA gene) biosynthesis. We investigated the effect of a HGT-acquired TrpF enzyme upon PriA's substrate specificity in Corynebacterium through comparative genomics and phylogenetic reconstructions. After comprehensive in vivo and enzyme kinetic analyses of selected PriA homologs, a novel (βα)8 isomerase subfamily with a specialized function in l-histidine biosynthesis, termed subHisA, was confirmed. X-ray crystallography was used to reveal active-site mutations in subHisA important for narrowing of substrate specificity, which when mutated to the naturally occurring amino acid in PriA led to gain of function. Moreover, in silico molecular dynamic analyses demonstrated that the narrowing of substrate specificity of subHisA is concomitant with loss of ancestral protein conformational states. Our results show the importance of HGT in shaping enzyme evolution and metabolism.

PubMed: 23800623
DOI: 10.1093/MOLBEV/MST115

Experimental method

X-RAY DIFFRACTION (2.25 Å)