1j49

INSIGHTS INTO DOMAIN CLOSURE, SUBSTRATE SPECIFICITY AND CATALYSIS OF D-LACTATE DEHYDROGENASE FROM LACTOBACILLUS BULGARICUS

spinqualitylabelsall models 1j49, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1j49 is a 2 chain structure with sequence from Lactobacillus delbrueckii subsp. bulgaricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: NAD, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LDHD_LACDA Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed NAD-dependent Lactobacillus bulgaricus D-Lactate dehydrogenase (D-LDHb) catalyses the reversible conversion of pyruvate into D-lactate. Crystals of D-LDHb complexed with NADH were grown and X-ray data collected to 2.2 A. The structure of D-LDHb was solved by molecular replacement using the dimeric Lactobacillus helveticus D-LDH as a model and was refined to an R-factor of 20.7%. The two subunits of the enzyme display strong asymmetry due to different crystal environments. The opening angles of the two catalytic domains with respect to the core coenzyme binding domains differ by 16 degrees. Subunit A is in an "open" conformation typical for a dehydrogenase apo enzyme and subunit B is "closed". The NADH-binding site in subunit A is only 30% occupied, while in subunit B it is fully occupied and there is a sulphate ion in the substrate-binding pocket. A pyruvate molecule has been modelled in the active site and its orientation is in agreement with existing kinetic and structural data. On domain closure, a cluster of hydrophobic residues packs tightly around the methyl group of the modelled pyruvate molecule. At least three residues from this cluster govern the substrate specificity. Substrate binding itself contributes to the stabilisation of domain closure and activation of the enzyme. In pyruvate reduction, D-LDH can adapt another protonated residue, a lysine residue, to accomplish the role of the acid catalyst His296. Required lowering of the lysine pK(a) value is explained on the basis of the H296K mutant structure. Domain closure, substrate specificity and catalysis of D-lactate dehydrogenase from Lactobacillus bulgaricus.,Razeto A, Kochhar S, Hottinger H, Dauter M, Wilson KS, Lamzin VS J Mol Biol. 2002 Apr 19;318(1):109-19. PMID:12054772 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lactate dehydrogenase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA