1J04

Structural mechanism of enzyme mistargeting in hereditary kidney stone disease in vitro

Summary for 1J04

• Entry DOI: 10.2210/pdb1j04/pdb
• Related: 1H0C
• Descriptor: alanine--glyoxylate aminotransferase, (AMINOOXY)ACETIC ACID, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase, aminotransferase, pyridoxal phosphate
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 44126.82

Authors

Zhang, X.,Djordjevic, S.,Bartlam, M.,Ye, S.,Rao, Z.,Danpure, C.J. (deposition date: 2002-10-30, release date: 2003-11-11, Last modification date: 2023-11-15)

Primary citation

Djordjevic, S.,Zhang, X.,Bartlam, M.,Ye, S.,Rao, Z.,Danpure, C.J.
Structural implications of a G170R mutation of alanine:glyoxylate aminotransferase that is associated with peroxisome-to-mitochondrion mistargeting.
Acta Crystallogr.,Sect.F, 66:233-236, 2010

PubMed Abstract: In a subset of patients with the hereditary kidney-stone disease primary hyperoxaluria type 1 (PH1), the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT) is mistargeted from peroxisomes to mitochondria. This is a consequence of the combined presence of the common P11L polymorphism and a disease-specific G170R mutation. In this paper, the crystal structure of mutant human AGT containing the G170R replacement determined at a resolution of 2.6 A is reported. The crystal structure of AGT consists of an intimate dimer in which an extended N-terminal segment of 21 amino acids from one subunit wraps as an elongated irregular coil around the outside of the crystallographic symmetry-related subunit. In addition to the N-terminal segment, the monomer structure contains a large domain of 261 amino acids and a small C-terminal domain of 110 amino acids. Comparison of the mutant AGT structure and that of wild-type normal AGT shows that the two structures are almost identical, with a backbone-atom r.m.s. deviation of 0.34 A. However, evidence of significant local structural changes in the vicinity of the G170R mutation might be linked to the apparent decrease in protein stability.

PubMed: 20208150
DOI: 10.1107/S1744309109054645

Experimental method

X-RAY DIFFRACTION (2.6 Å)