2VP8

Structure of Mycobacterium tuberculosis Rv1207

Summary for 2VP8

• Entry DOI: 10.2210/pdb2vp8/pdb
• Descriptor: DIHYDROPTEROATE SYNTHASE 2, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: dihydropteroate synthase, mycobacterium tuberculosis, rv1207, transferase, folate biosynthesis, antibiotic resistance
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 2
• Total formula weight: 66355.58

Authors

Gengenbacher, M.,Xu, T.,Niyomwattanakit, P.,Spraggon, G.,Dick, T. (deposition date: 2008-02-27, release date: 2008-08-12, Last modification date: 2023-12-13)

Primary citation

Gengenbacher, M.,Xu, T.,Niyomwattanakit, P.,Spraggon, G.,Dick, T.
Biochemical and Structural Characterization of the Putative Dihydropteroate Synthase Ortholog Rv1207 of Mycobacterium Tuberculosis.
Fems Microbiol.Lett., 287:128-, 2008

PubMed Abstract: Dihydropteroate synthase (DHPS) is involved in de novo biosynthesis of the essential cofactor folate by catalyzing the condensation of para-aminobenzoic acid (pABA) and 6-hydroxymethyl-7,8-dihydropterin-pyrophosphate (H2PtPP). Mycobacterium tuberculosis possesses a functional DHPS (MtDHPS, Rv3608c, folP1) and, based on sequence similarities, a putative ortholog (Rv1207, folP2). Here, we demonstrate that Rv1207 shows a low H2PtPP substrate affinity and lacks enzymatic DHPS activity. However, we found dapsone, a structural analog of pABA and clinically used DHPS inhibitor, to weakly bind both proteins. To gain insights into the lack of DHPS activity of Rv1207, its three-dimensional structure was determined at 2.64 A. The overall fold of both, MtDHPS (1EYE) and Rv1207, is highly conserved and conforms to a classical triosephosphate isomerase barrel arrangement. The predicted H2PtPP-binding pocket of Rv1207 is occupied by a histidine side chain, relative to a leucine residue in MtDHPS, consistent with the low affinity for this substrate and the lack of DHPS activity. We conclude that folP2 does not encode a DHPS and therefore cannot act as bypass for folP1. The metabolic function of Rv1207 remains to be defined.

PubMed: 18680522
DOI: 10.1111/J.1574-6968.2008.01302.X

Experimental method

X-RAY DIFFRACTION (2.64 Å)