1h0c
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THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE
OverviewOverview
A deficiency of the liver-specific enzyme alanine:glyoxylate, aminotransferase (AGT) is responsible for the potentially lethal, hereditary kidney stone disease primary hyperoxaluria type 1 (PH1). Many, of the mutations in the gene encoding AGT are associated with specific, enzymatic phenotypes such as accelerated proteolysis (Ser205Pro), intra-peroxisomal aggregation (Gly41Arg), inhibition of pyridoxal, phosphate binding and loss of catalytic activity (Gly82Glu), and, peroxisome-to-mitochondrion mistargeting (Gly170Arg). Several mutations, including that responsible for AGT mistargeting, co-segregate and interact, synergistically with a Pro11Leu polymorphism found at high frequency in, the normal population. In order to gain further insights into the, mechanistic link between genotype and enzymatic phenotype in PH1, we have, determined the crystal structure of normal human AGT complexed to the, competitive inhibitor amino-oxyacetic acid to 2.5A. Analysis of this, structure allows the effects of these mutations and polymorphism to be, rationalised in terms of AGT tertiary and quaternary conformation, and in, particular it provides a possible explanation for the Pro11Leu-Gly170Arg, synergism that leads to AGT mistargeting.
About this StructureAbout this Structure
1H0C is a Single protein structure of sequence from Homo sapiens with PLP, AOA and GOL as ligands. Active as Alanine--glyoxylate transaminase, with EC number 2.6.1.44 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1., Zhang X, Roe SM, Hou Y, Bartlam M, Rao Z, Pearl LH, Danpure CJ, J Mol Biol. 2003 Aug 15;331(3):643-52. PMID:12899834
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