Document Detail


Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV.
MedLine Citation:
PMID:  20977429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Qian Han; Howard Robinson; Tao Cai; Danilo A Tagle; Jianyong Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Bioscience reports     Volume:  31     ISSN:  1573-4935     ISO Abbreviation:  Biosci. Rep.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-04-26     Completed Date:  2012-03-26     Revised Date:  2012-10-09    
Medline Journal Info:
Nlm Unique ID:  8102797     Medline TA:  Biosci Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  323-32     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
NS062836/NS/NINDS NIH HHS; R01 NS062836/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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