1EKP

CRYSTAL STRUCTURE OF HUMAN BRANCHED CHAIN AMINO ACID AMINOTRANSFERASE (MITOCHONDRIAL) COMPLEXED WITH PYRIDOXAL-5'-PHOSPHATE AT 2.5 ANGSTROMS (MONOCLINIC FORM).

Summary for 1EKP

• Entry DOI: 10.2210/pdb1ekp/pdb
• Related: 1EKF 1EKV
• Descriptor: BRANCHED CHAIN AMINO ACID AMINOTRANSFERASE (MITOCHONDRIAL), PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: fold type iv, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform A: Mitochondrion. Isoform B: Cytoplasm: O15382
• Total number of polymer chains: 2
• Total formula weight: 83230.32

Authors

Yennawar, N.H.,Dunbar, J.H.,Conway, M.,Hutson, S.M.,Farber, G.K. (deposition date: 2000-03-09, release date: 2001-03-09, Last modification date: 2024-04-03)

Primary citation

Yennawar, N.,Dunbar, J.,Conway, M.,Hutson, S.,Farber, G.
The structure of human mitochondrial branched-chain aminotransferase.
Acta Crystallogr.,Sect.D, 57:506-515, 2001

PubMed Abstract: X-ray crystal structures of three forms of human mitochondrial branched-chain aminotransferase (BCAT) were solved by molecular-replacement methods, using Escherichia coli BCAT as the search model. The enzyme is a homodimer and the polypeptide chain of each monomer has two domains. The small domain is composed of residues 1--175 and the large domain is composed of residues 176--365. The active site is close to the dimer interface. The 4'-aldehyde of the PLP cofactor is covalently linked to the epsilon-amino group of the active-site lysine, Lys202, via a Schiff-base linkage in two of the structures. In the third structure, the enzyme is irreversibly inactivated by Tris. The overall fold of the dimer in human mitochondrial BCAT is similar to the structure of two bacterial enzymes, E. coli BCAT and D-amino acid aminotransferase (D-AAT). The residues lining the putative substrate-binding pocket of human BCAT and D-AAT are completely rearranged to allow catalysis with substrates of opposite stereochemistry. In the case of human mitochondrial branched-chain aminotransferase, a hydrogen-bond interaction between the guanidinium group of Arg143 in the first monomer with the side-chain hydroxyl of Tyr70 in the second monomer is important in the formation of the substrate-binding pocket.

PubMed: 11264579
DOI: 10.1107/S0907444901001925

Experimental method

X-RAY DIFFRACTION (2.5 Å)