9cp9
Crystal structure of DHPS-3-dehydrogenase, HpsN H319A variant from Cupriavidus pinatubonensis in complex with substrate (R-DHPS) and NADH
Structural highlights
FunctionHPSN_CUPPJ Catalyzes the NAD-dependent oxidation of (R)-2,3-dihydroxypropane-1-sulfonate to (R)-3-sulfolactate.[1] Publication Abstract from PubMed2,3-Dihydroxypropanesulfonate (DHPS) and sulfolactate (SL) are environmentally important organosulfur compounds that play key roles as metabolic currencies in the sulfur cycle. Despite their prevalence, the pathways governing DHPS and SL production remain poorly understood. Here, we study DHPS-3-dehydrogenase from Cupriavidus pinatubonensis (CpHpsN), a bacterium capable of utilizing DHPS as a sole carbon source. Kinetic analysis of CpHpsN reveals a strict preference for R-DHPS, catalyzing its 4-electron oxidation to R-SL, with high specificity for NAD(+) over NADP(+). The 3D structure of CpHpsN in complex with Zn(2+), NADH and R-SL, elucidated through X-ray crystallography, reveals a fold akin to bacterial and plant histidinol dehydrogenases with similar coordination geometry around the octahedral Zn(2+) centre and involving the sulfonate group as a ligand. A key residue, His126, distinguishes DHPS dehydrogenases from histidinol dehydrogenases, by structural recognition of the sulfonate substrate of the former. Site-directed mutagenesis pinpoints Glu318, His319, and Asp352 as active-site residues important for the catalytic activity of CpHpsN. Taxonomic and pathway distribution analysis reveals the prevalence of HpsN homologues within different pathways of DHPS catabolism and across bacterial classes including Alpha-, Beta-, Gamma-, and Deltaproteobacteria and Desulfobacteria, emphasizing its importance in the biogeochemical sulfur cycle. Structural and kinetic insights into the stereospecific oxidation of R-2,3-dihydroxypropanesulfonate by DHPS-3-dehydrogenase from Cupriavidus pinatubonensis.,Burchill L, Kaur A, Nastasovici A, Lee M, Williams SJ Chem Sci. 2024 Sep 9. doi: 10.1039/d4sc05114a. PMID:39263660[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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