2hhf: Difference between revisions
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[[Image:2hhf.jpg|left|200px]] | [[Image:2hhf.jpg|left|200px]] | ||
'''X-ray crystal structure of oxidized human mitochondrial branched chain aminotransferase (hBCATm)''' | {{Structure | ||
|PDB= 2hhf |SIZE=350|CAPTION= <scene name='initialview01'>2hhf</scene>, resolution 1.800Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID'>EPE</scene> | |||
|ACTIVITY= [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] | |||
|GENE= BCAT2, BCATM, ECA40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''X-ray crystal structure of oxidized human mitochondrial branched chain aminotransferase (hBCATm)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2HHF is a [ | 2HHF is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HHF OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17050531 17050531] | ||
[[Category: Branched-chain-amino-acid transaminase]] | [[Category: Branched-chain-amino-acid transaminase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: PLP]] | [[Category: PLP]] | ||
[[Category: d-aminoacid aminotransferase-like plp-dependent | [[Category: d-aminoacid aminotransferase-like plp-dependent enzyme]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:17:07 2008'' | ||
Revision as of 18:17, 20 March 2008
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| , resolution 1.800Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | BCAT2, BCATM, ECA40 (Homo sapiens) | ||||||
| Activity: | Branched-chain-amino-acid transaminase, with EC number 2.6.1.42 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
DiseaseDisease
Known diseases associated with this structure: Hypervalinemia or hyperleucine-isoleucinemia (1) OMIM:[113530]
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
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