4IT9

Structure of Bacterial Enzyme

Summary for 4IT9

• Entry DOI: 10.2210/pdb4it9/pdb
• Related: 4ITA 4ITB
• Descriptor: Succinate-semialdehyde dehydrogenase, 1,2-ETHANEDIOL, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Synechococcus sp.
• Total number of polymer chains: 2
• Total formula weight: 100632.43

Authors

Rhee, S.,Park, J. (deposition date: 2013-01-18, release date: 2013-04-24, Last modification date: 2024-02-28)

Primary citation

Park, J.,Rhee, S.
Structural Basis for a Cofactor-dependent Oxidation Protection and Catalysis of Cyanobacterial Succinic Semialdehyde Dehydrogenase.
J.Biol.Chem., 288:15760-15770, 2013

PubMed Abstract: Succinic semialdehyde dehydrogenase (SSADH) from cyanobacterium Synechococcus differs from other SSADHs in the γ-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.

PubMed: 23589281
DOI: 10.1074/jbc.M113.460428

Experimental method

X-RAY DIFFRACTION (1.7 Å)