1H0C

The crystal structure of human alanine:glyoxylate aminotransferase

Summary for 1H0C

• Entry DOI: 10.2210/pdb1h0c/pdb
• Descriptor: SERINE--GLYOXYLATE AMINOTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE, (AMINOOXY)ACETIC ACID, ... (5 entities in total)
• Functional Keywords: aminotransferase, pyridoxal phosphate, transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 43953.61

Authors

Zhang, X.,Danpure, C.J.,Roe, S.M.,Pearl, L.H. (deposition date: 2002-06-17, release date: 2003-06-12, Last modification date: 2025-04-09)

Primary citation

Zhang, X.,Roe, S.M.,Roe, S.M.,Hou, Y.,Bartlam, M.,Rao, Z.,Pearl, L.H.,Danpure, C.J.
Crystal Structure of Alanine:Glyoxylate Aminotransferase and the Relationship between Genotype and Enzymatic Phenotype in Primary Hyperoxaluria Type 1.
J.Mol.Biol., 331:643-, 2003

PubMed Abstract: 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.

PubMed: 12899834
DOI: 10.1016/S0022-2836(03)00791-5

Experimental method

X-RAY DIFFRACTION (2.5 Å)