Dataset

The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+ / enzyme interactions

Monash University
Dr Ashley Buckle (Managed by)
Viewed: [[ro.stat.viewed]] Cited: [[ro.stat.cited]] Accessed: [[ro.stat.accessed]]
ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rfr_id=info%3Asid%2FANDS&rft_id=hdl:102.100.100/42&rft.title=The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+ / enzyme interactions&rft.identifier=3JZ4&rft.publisher=Monash University&rft.description=&rft.creator=Anonymous&rft.date=2010&rft_subject=Biochemistry and Cell Biology&rft_subject=Biological Sciences&rft_subject=Medical Biochemistry and Metabolomics&rft_subject=Medical and Health Sciences&rft_subject=Macromolecular Crystallography&rft_subject=Diffraction&rft_subject=Protein Structure&rft_subject=X-Ray&rft_subject=Synchrotron&rft.type=dataset&rft.language=English Go to Data Provider

Contact Information

Monash University

About

In mammals succinic semialdehyde dehydrogenase (SSADH) plays an essential role in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) to succinic acid (SA). Deficiency of SSADH in humans results in elevated levels of GABA and γ-Hydroxybutyric acid (GHB) which leads to psychomotor retardation, muscular hypotonia, non-progressive ataxia and seizures. In Escherichia coli, two genetically distinct forms of SSADHs had been described which are essential for preventing accumulation of toxic levels of succinic semialdehyde (SSA) in cells. Here we structurally characterise SSADH encoded by the E coli gabD gene and compare these data with the structure of human SSADH. Interestingly, in contrast to the human enzyme in the E. coli SSADH structure, electron density for the complete NADP+ cofactor in the binding sites is clearly evident; these data in particular revealing how the nicotinamide ring of the co-facto is positioned in each active site. Furthermore, our structural data suggest that a deletion of three amino acids in E. coli SSADH permits this enzyme to use NADP+ whereas in contrast the human enzyme utilises NAD+. Finally, the structure of E. coli SSADH gives additional insight into human mutations that result in disease.
Subjects

User Contributed Tags    

Login to tag this record with meaningful keywords to make it easier to discover

Other Information
Identifiers