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Structure of bacterial enzyme in complex with cofactor
Structural highlights
FunctionPublication Abstract from PubMedSuccinic semialdehyde dehydrogenase (SSADH) from cyanobacterium Synechococcus differs from other SSADHs in the gamma-aminobutyrate shunt. Synechococcus SSADH (SySSADH) is a TCA cycle enzyme and completes a 2-oxoglutarate dehydrogenase-deficient cyanobacterial TCA cycle through a detour metabolic pathway. SySSADH produces succinate in an NADP(+)-dependent manner with a single cysteine acting as the catalytic residue in the catalytic loop. Crystal structures of SySSADH were determined in their apo form, as a binary complex with NADP(+) and as a ternary complex with succinic semialdehyde and NADPH, providing details about the catalytic mechanism by revealing a covalent adduct of a cofactor with the catalytic cysteine in the binary complex and a proposed thiohemiacetal intermediate in the ternary complex. Further analyses showed that SySSADH is an oxidation-sensitive enzyme and that the formation of the NADP-cysteine adduct is a kinetically preferred event that protects the catalytic cysteine from H2O2-dependent oxidative stress. These structural and functional features of SySSADH provide a molecular basis for cofactor-dependent oxidation protection in 1-Cys SSADH, which is unique relative to other 2-Cys SSADHs employing a redox-dependent formation of a disulfide bridge. Structural Basis for a Cofactor-dependent Oxidation Protection and Catalysis of Cyanobacterial Succinic Semialdehyde Dehydrogenase.,Park J, Rhee S J Biol Chem. 2013 May 31;288(22):15760-70. doi: 10.1074/jbc.M113.460428. Epub, 2013 Apr 15. PMID:23589281[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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