| Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV. | |
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MedLine Citation:
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PMID: 20977429 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mammalian mAspAT (mitochondrial aspartate aminotransferase) is recently reported to have KAT (kynurenine aminotransferase) activity and plays a role in the biosynthesis of KYNA (kynurenic acid) in rat, mouse and human brains. This study concerns the biochemical and structural characterization of mouse mAspAT. In this study, mouse mAspAT cDNA was amplified from mouse brain first stand cDNA and its recombinant protein was expressed in an Escherichia coli expression system. Sixteen oxo acids were tested for the co-substrate specificity of mouse mAspAT and 14 of them were shown to be capable of serving as co-substrates for the enzyme. Structural analysis of mAspAT by macromolecular crystallography revealed that the cofactor-binding residues of mAspAT are similar to those of other KATs. The substrate-binding residues of mAspAT are slightly different from those of other KATs. Our results provide a biochemical and structural basis towards understanding the overall physiological role of mAspAT in vivo and insight into controlling the levels of endogenous KYNA through modulation of the enzyme in the mouse brain. |
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Authors:
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Qian Han; Howard Robinson; Tao Cai; Danilo A Tagle; Jianyong Li |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Bioscience reports Volume: 31 ISSN: 1573-4935 ISO Abbreviation: Biosci. Rep. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-04-26 Completed Date: 2012-03-26 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 8102797 Medline TA: Biosci Rep Country: United States |
Other Details:
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Languages: eng Pagination: 323-32 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aspartate Aminotransferase, Mitochondrial / chemistry*, genetics Brain / enzymology Crystallography, X-Ray / methods Enzyme Activation / physiology Kynurenic Acid / metabolism* Mice Mitochondrial Proteins / chemistry*, genetics Transaminases / chemistry*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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NS062836/NS/NINDS NIH HHS; R01 NS062836/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Mitochondrial Proteins; 492-27-3/Kynurenic Acid; EC 2.6.1.-/Aspartate Aminotransferase, Mitochondrial; EC 2.6.1.-/Transaminases; EC 2.6.1.7/kynurenine-oxoglutarate transaminase |
| Comments/Corrections | |
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