5us6 | pdb_00005us6

Structure of Dihydrodipicolinate Reductase from Vibrio vulnificus Bound to NADH and 2,6 Pyridine Dicarboxylic Acid with Intact Polyhistidine Tag

spinqualitylabelsall models 5us6, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5us6 is a 12 chain structure with sequence from Vibvu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAD, PDC, SO4 Gene: dapB, VV1_0567 (VIBVU) Activity: 4-hydroxy-tetrahydrodipicolinate reductase, with EC number 1.17.1.8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DAPB_VIBVU] Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate.[HAMAP-Rule:MF_00102] Publication Abstract from PubMed BACKGROUND: The products of the lysine biosynthesis pathway, meso-diaminopimelate and lysine, are essential for bacterial survival. This paper focuses on the structural and mechanistic characterization of 4-hydroxy-tetrahydrodipicolinate reductase (DapB), which is one of the enzymes from the lysine biosynthesis pathway. DapB catalyzes the conversion of (2S, 4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate (HTPA) to 2,3,4,5-tetrahydrodipicolinate in an NADH/NADPH dependent reaction. Genes coding for DapBs were identified as essential for many pathogenic bacteria, and therefore DapB is an interesting new target for the development of antibiotics. METHODS: We have combined experimental and computational approaches to provide novel insights into mechanism of the DapB catalyzed reaction. RESULTS: Structures of DapBs originating from Mycobacterium tuberculosis and Vibrio vulnificus in complexes with NAD(+), NADP(+), as well as with inhibitors, were determined and described. The structures determined by us, as well as currently available structures of DapBs from other bacterial species, were compared and used to elucidate a mechanism of reaction catalyzed by this group of enzymes. Several different computational methods were used to provide a detailed description of a plausible reaction mechanism. CONCLUSIONS: This is the first report presenting the detailed mechanism of reaction catalyzed by DapB. GENERAL SIGNIFICANCE: Structural data in combination with information on the reaction mechanism provide a background for development of DapB inhibitors, including transition-state analogues. Comparative structural and mechanistic studies of 4-hydroxy-tetrahydrodipicolinate reductases from Mycobacterium tuberculosis and Vibrio vulnificus.,Pote S, Kachhap S, Mank NJ, Daneshian L, Klapper V, Pye S, Arnette AK, Shimizu LS, Borowski T, Chruszcz M Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129750. doi:, 10.1016/j.bbagen.2020.129750. Epub 2020 Sep 24. PMID:32980502 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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