4ihi | pdb_00004ihi

Crystal structure of the Delta-pyrroline-5-carboxylate dehydrogenase from Mycobacterium tuberculosis bound with NAD

spinqualitylabelsall models 4ihi, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ihi is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAD Related: 4idm, 4ids Gene: MT1224, pruA, rocA, Rv1187 (MYCTU) Activity: 1-pyrroline-5-carboxylate dehydrogenase, with EC number 1.5.1.12 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The proline-utilization pathway in Mycobacterium tuberculosis (Mtb) has recently been identified as an important factor in Mtb persistence in vivo, suggesting that this pathway could be a valuable therapeutic target against tuberculosis (TB). In Mtb, two distinct enzymes perform the conversion of proline into glutamate: the first step is the oxidation of proline into Delta(1)-pyrroline-5-carboxylic acid (P5C) by the flavoenzyme proline dehydrogenase (PruB), and the second reaction involves converting the tautomeric form of P5C (glutamate-gamma-semialdehyde) into glutamate using the NAD(+)-dependent Delta(1)-pyrroline-5-carboxylic dehydrogenase (PruA). Here, the three-dimensional structures of Mtb-PruA, determined by X-ray crystallography, in the apo state and in complex with NAD(+) are described at 2.5 and 2.1 A resolution, respectively. The structure reveals a conserved NAD(+)-binding mode, common to other related enzymes. Species-specific conformational differences in the active site, however, linked to changes in the dimer interface, suggest possibilities for selective inhibition of Mtb-PruA despite its reasonably high sequence identity to other PruA enzymes. Using recombinant PruA and PruB, the proline-utilization pathway in Mtb has also been reconstituted in vitro. Functional validation using a novel NMR approach has demonstrated that the PruA and PruB enzymes are together sufficient to convert proline to glutamate, the first such demonstration for monofunctional proline-utilization enzymes. Characterization of the proline-utilization pathway in Mycobacterium tuberculosis through structural and functional studies.,Lagautriere T, Bashiri G, Paterson NG, Berney M, Cook GM, Baker EN Acta Crystallogr D Biol Crystallogr. 2014 Apr 1;70(Pt 4):968-80. doi:, 10.1107/S1399004713034391. Epub 2014 Mar 19. PMID:24699642 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyrroline-5-carboxylate dehydrogenase

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