2E1Q

Crystal Structure of Human Xanthine Oxidoreductase mutant, Glu803Val

2E1Q の概要

• エントリーDOI: 10.2210/pdb2e1q/pdb
• 分子名称: Xanthine dehydrogenase/oxidase, BICARBONATE ION, CALCIUM ION, ... (9 entities in total)
• 機能のキーワード: xanthine oxidase, molybdenum cofactor, fad, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P47989
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 594114.32

構造登録者

Yamaguchi, Y.,Matsumura, T.,Ichida, K.,Okamoto, K.,Nishino, T. (登録日: 2006-10-27, 公開日: 2007-09-18, 最終更新日: 2023-10-25)

主引用文献

Yamaguchi, Y.,Matsumura, T.,Ichida, K.,Okamoto, K.,Nishino, T.
Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate
J.Biochem.(Tokyo), 141:513-524, 2007

PubMed Abstract: Xanthine oxidase (oxidoreductase; XOR) and aldehyde oxidase (AO) are similar in protein structure and prosthetic group composition, but differ in substrate preference. Here we show that mutation of two amino acid residues in the active site of human XOR for purine substrates results in conversion of the substrate preference to AO type. Human XOR and its Glu803-to-valine (E803V) and Arg881-to-methionine (R881M) mutants were expressed in an Escherichia coli system. The E803V mutation almost completely abrogated the activity towards hypoxanthine as a substrate, but very weak activity towards xanthine remained. On the other hand, the R881M mutant lacked activity towards xanthine, but retained slight activity towards hypoxanthine. Both mutants, however, exhibited significant aldehyde oxidase activity. The crystal structure of E803V mutant of human XOR was determined at 2.6 A resolution. The overall molybdopterin domain structure of this mutant closely resembles that of bovine milk XOR; amino acid residues in the active centre pocket are situated at very similar positions and in similar orientations, except that Glu803 was replaced by valine, indicating that the decrease in activity towards purine substrate is not due to large conformational change in the mutant enzyme. Unlike wild-type XOR, the mutants were not subject to time-dependent inhibition by allopurinol.

PubMed: 17301077
DOI: 10.1093/jb/mvm053

実験手法

X-RAY DIFFRACTION (2.6 Å)