2hhf: Difference between revisions

Revision as of 06:17, 4 May 2008

X-ray crystal structure of oxidized human mitochondrial branched chain aminotransferase (hBCATm)

OverviewOverview

Mammalian branched chain aminotransferases (BCATs) have a unique CXXC center. Kinetic and structural studies of three CXXC center mutants (C315A, C318A, and C315A/C318A) of human mitochondrial (hBCATm) isozyme and the oxidized hBCATm enzyme (hBCATm-Ox) have been used to elucidate the role of this center in hBCATm catalysis. X-ray crystallography revealed that the CXXC motif, through its network of hydrogen bonds, plays a crucial role in orienting the substrate optimally for catalysis. In all structures, there were changes in the structure of the beta-turn preceding the CXXC motif when compared with wild type protein. The N-terminal loop between residues 15 and 32 is flexible in the oxidized and mutant enzymes, the disorder greater in the oxidized protein. Disordering of the N-terminal loop disrupts the integrity of the side chain binding pocket, particularly for the branched chain side chain, less so for the dicarboxylate substrate side chain. The kinetic studies of the mutant and oxidized enzymes support the structural analysis. The kinetic results showed that the predominant effect of oxidation was on the second half-reaction rather than the first half-reaction. The oxidized enzyme was completely inactive, whereas the mutants showed limited activity. Model building of the second half-reaction substrate alpha-ketoisocaproate in the pyridoxamine 5'-phosphate-hBCATm structure suggests that disruption of the CXXC center results in altered substrate orientation and deprotonation of the amino group of pyridoxamine 5'-phosphate, which inhibits catalysis.

About this StructureAbout this Structure

2HHF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Human mitochondrial branched chain aminotransferase isozyme: structural role of the CXXC center in catalysis., Yennawar NH, Islam MM, Conway M, Wallin R, Hutson SM, J Biol Chem. 2006 Dec 22;281(51):39660-71. Epub 2006 Oct 18. PMID:17050531 Page seeded by OCA on Sun May 4 06:17:54 2008

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OCA

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 [[Image:2hhf.jpg|left|200px]]
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </span>
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-|GENE= BCAT2, BCATM, ECA40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-|DOMAIN=
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hhf OCA], [http://www.ebi.ac.uk/pdbsum/2hhf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hhf RCSB]</span>
-}}
 '''X-ray crystal structure of oxidized human mitochondrial branched chain aminotransferase (hBCATm)'''
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 [[Category: Hutson, S M.]]
 [[Category: Yennawar, N H.]]
-[[Category: d-aminoacid aminotransferase-like plp-dependent enzyme]]
+[[Category: D-aminoacid aminotransferase-like plp-dependent enzyme]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 06:17:54 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:30:29 2008''