4ITA: Structure Of Bacterial Enzyme In Complex With Cofactor

Citation:
Abstract
Succinic 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.
PDB ID: 4ITADownload
MMDB ID: 109434
PDB Deposition Date: 2013/1/18
Updated in MMDB: 2013/06
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4ITA: dimeric; determined by author and by software (PISA)
Molecular Components in 4ITA
Label Count Molecule
Proteins (2 molecules)
2
Succinate-semialdehyde Dehydrogenase
Molecule annotation
Chemicals (36 molecules)
1
2
2
34
* Click molecule labels to explore molecular sequence information.

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