1h0c

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{{STRUCTURE_1h0c| PDB=1h0c | SCENE= }}
{{STRUCTURE_1h0c| PDB=1h0c | SCENE= }}
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'''THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE'''
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===THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12899834 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12899834}}
==About this Structure==
==About this Structure==
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[[Category: Pyridoxal phosphate]]
[[Category: Pyridoxal phosphate]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:24:42 2008''

Revision as of 03:24, 1 July 2008

Image:1h0c.png

Template:STRUCTURE 1h0c

THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE

Template:ABSTRACT PUBMED 12899834

About this Structure

1H0C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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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