1kta

HUMAN BRANCHED CHAIN AMINO ACID AMINOTRANSFERASE : THREE DIMENSIONAL STRUCTURE OF THE ENZYME IN ITS PYRIDOXAMINE PHOSPHATE FORM.HUMAN BRANCHED CHAIN AMINO ACID AMINOTRANSFERASE : THREE DIMENSIONAL STRUCTURE OF THE ENZYME IN ITS PYRIDOXAMINE PHOSPHATE FORM.

Structural highlights 1kta is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 1ekf, 1ekv, 1ekp, 1kt8 Activity: Branched-chain-amino-acid transaminase, with EC number 2.6.1.42 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BCAT2_HUMAN] Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The three-dimensional structures of the isoleucine ketimine and the pyridoxamine phosphate forms of human mitochondrial branched chain aminotransferase (hBCATm) have been determined crystallographically at 1.9 A resolution. The hBCATm-catalyzed transamination can be described in molecular terms together with the earlier solved pyridoxal phosphate forms of the enzyme. The active site lysine, Lys202, undergoes large conformational changes, and the pyridine ring of the cofactor tilts by about 18 degrees during catalysis. A major determinant of the enzyme's substrate and stereospecificity for L-branched chain amino acids is a group of hydrophobic residues that form three hydrophobic surfaces and lock the side chain in place. Short-chain aliphatic amino acid side chains are unable to interact through van der Waals contacts with any of the surfaces whereas bulky aromatic side chains would result in significant steric hindrance. As shown by modeling, and in agreement with previous biochemical data, glutamate but not aspartate can form hydrogen bond interactions. The carboxylate group of the bound isoleucine is on the same side as the phosphate group of the cofactor. These active site interactions are largely retained in a model of the human cytosolic branched chain aminotransferase (hBCATc), suggesting that residues in the second tier of interactions are likely to determine the specificity of hBCATc for the drug gabapentin. Finally, the structures reveal a unique role for cysteine residues in the mammalian BCAT. Cys315 and Cys318, which immediately follow a beta-turn (residues 311-314) and are located just outside the active site, form an unusual thiol-thiolate hydrogen bond. This beta-turn positions Thr313 for its interaction with the pyridoxal phosphate oxygens and substrate alpha-carboxylate group. Crystal structures of human mitochondrial branched chain aminotransferase reaction intermediates: ketimine and pyridoxamine phosphate forms.,Yennawar NH, Conway ME, Yennawar HP, Farber GK, Hutson SM Biochemistry. 2002 Oct 1;41(39):11592-601. PMID:12269802 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminotransferase

spinqualitylabelsall models 1kta, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image