Structural studies of the catalytic reaction pathway of a hyperthermophilic histidinol-phosphate aminotransferase.
In histidine biosynthesis, histidinol-phosphate aminotransferase catalyzes the transfer of the amino group from glutamate to imidazole acetol-phosphate producing 2-oxoglutarate and histidinol phosphate. In some organisms such as the hyperthermophile Thermotoga maritima, specific tyrosine and aromatic amino acid transaminases have not been identified to date, suggesting an additional role for histidinol-phosphate aminotransferase in other transamination reactions generating aromatic amino acids. To gain insight into the specific function of this transaminase, we have determined its crystal structure in the absence of any ligand except phosphate, in the presence of covalently bound pyridoxal 5'-phosphate, of the coenzyme histidinol phosphate adduct, and of pyridoxamine 5'-phosphate. The enzyme accepts histidinol phosphate, tyrosine, tryptophan, and phenylalanine, but not histidine, as substrates. The structures provide a model of how these different substrates could be accommodated by histidinol-phosphate aminotransferase. Some of the structural features of the enzyme are more preserved between the T. maritima enzyme and a related threonine-phosphate decarboxylase from S. typhimurium than with histidinol-phosphate aminotransferases from different organisms.
EMBL c/o Deutsches Elektronen-Synchrotron, Notkestrasse 85, Building 25A, D-22603 Hamburg, Germany.
Francisco J
FJ
Fernandez
M Cristina
MC
Vega
Frank
F
Lehmann
Erika
E
Sandmeier
Heinz
H
Gehring
Philipp
P
Christen
Matthias
M
Wilmanns
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D002384:Catalysis; D017931:DNA Primers; D004795:Enzyme Stability; D006358:Hot Temperature; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D020124:Thermotoga maritima / Q000201:enzymology; D000637:Transaminases / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection
D001426:Bacterial Proteins; D017931:DNA Primers; D011994:Recombinant Proteins; D000637:Transaminases; C053430:histidinol-phosphate aminotransferase