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Title: Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV

Abstract

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:
; ; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
DOE - OFFICE OF SCIENCE
OSTI Identifier:
1034085
Report Number(s):
BNL-96552-2011-JA
Journal ID: ISSN 0144-8463; BRPTDT; R&D Project: BO-070; KP1605010; TRN: US201203%%385
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Bioscience Reports
Additional Journal Information:
Journal Volume: 31; Journal Issue: 5; Journal ID: ISSN 0144-8463
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; BIOSYNTHESIS; BRAIN; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; ENZYMES; ESCHERICHIA COLI; HETEROCYCLIC ACIDS; HYDROXY COMPOUNDS; IN VIVO; KYNURENINE; MICE; MODULATION; PROTEINS; QUINOLINES; RESIDUES; SPECIFICITY; aspartate aminotransferase; crystal structure; oxo acid; kynurenic acid; kynurenine; kynurenine aminotransferase

Citation Formats

Han, Q., Robinson, H., Cai, T., Tagle, D. A., and Li, J. Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV. United States: N. p., 2011. Web. doi:10.1042/BSR20100117.
Han, Q., Robinson, H., Cai, T., Tagle, D. A., & Li, J. Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV. United States. doi:10.1042/BSR20100117.
Han, Q., Robinson, H., Cai, T., Tagle, D. A., and Li, J. Sat . "Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV". United States. doi:10.1042/BSR20100117.
@article{osti_1034085,
title = {Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV},
author = {Han, Q. and Robinson, H. and Cai, T. and Tagle, D. A. and Li, J.},
abstractNote = {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.},
doi = {10.1042/BSR20100117},
journal = {Bioscience Reports},
issn = {0144-8463},
number = 5,
volume = 31,
place = {United States},
year = {2011},
month = {10}
}