4itb
Structure of bacterial enzyme in complex with cofactor and substrateStructure of bacterial enzyme in complex with cofactor and substrate
Structural highlights
Publication 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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