2ZZ2

Orotidine Monophosphate Decarboxylase K72A mutant from M. thermoautotrophicum complexed with 6-cyano-UMP

2ZZ2 の概要

• エントリーDOI: 10.2210/pdb2zz2/pdb
• 関連するPDBエントリー: 1DV7 1LOR 1LOS 1LP6 1X1Z 2E6Y 2ZZ1 2ZZ3 2ZZ4 2ZZ5 2ZZ6 2ZZ7
• 分子名称: Orotidine 5'-phosphate decarboxylase, 6-cyanouridine 5'-phosphate, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: orotidine 5'-monophosphate decarboxylase (odcase), 6-cyanoump omp decarboxylase, ompdc, ompdcase, decarboxylase, lyase, pyrimidine biosynthesis
• 由来する生物種: Methanothermobacter thermautotrophicus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55709.36

構造登録者

Fujihashi, M.,Pai, E.F. (登録日: 2009-02-05, 公開日: 2009-03-24, 最終更新日: 2023-11-01)

主引用文献

Fujihashi, M.,Wei, L.,Kotra, L.P.,Pai, E.F.
Structural characterization of the molecular events during a slow substrate-product transition in orotidine 5'-monophosphate decarboxylase
J.Mol.Biol., 387:1199-1210, 2009

PubMed Abstract: Crystal structures of substrate-product complexes of Methanobacterium thermoautotrophicum orotidine 5'-monophosphate decarboxylase, obtained at various steps in its catalysis of the unusual transformation of 6-cyano-uridine 5'-monophosphate (UMP) into barbituric acid ribosyl monophosphate, show that the cyano substituent of the substrate, when bound to the active site, is first bent significantly from the plane of the pyrimidine ring and then replaced by an oxygen atom. Although the K72A and D70A/K72A mutants are either catalytically impaired or even completely inactive, they still display bending of the C6 substituent. Interestingly, high-resolution structures of the D70A and D75N mutants revealed a covalent bond between C6 of UMP and the Lys72 side chain after the -CN moiety's release. The same covalent bond was observed when the native enzyme was incubated with 6-azido-UMP and 6-iodo-UMP; in contrast, the K72A mutant transformed 6-iodo-UMP to barbituric acid ribosyl 5'-monophosphate. These results demonstrate that, given a suitable environment, native orotidine 5'-monophosphate decarboxylase and several of its mutants are not restricted to the physiologically relevant decarboxylation; they are able to catalyze even nucleophilic substitution reactions but consistently maintain distortion on the C6 substituent as an important feature of catalysis.

PubMed: 19236876
DOI: 10.1016/j.jmb.2009.02.037

実験手法

X-RAY DIFFRACTION (1.53 Å)