2GEB

Crystal structure of the Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase L160I mutant: insights into the inhibitor design

2GEB の概要

• エントリーDOI: 10.2210/pdb2geb/pdb
• 関連するPDBエントリー: 1R3U 1YFZ
• 分子名称: Hypoxanthine-guanine phosphoribosyltransferase, CALCIUM ION (3 entities in total)
• 機能のキーワード: hgprt, mutant, inhibitor design, selectivity, transferase
• 由来する生物種: Thermoanaerobacter tengcongensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20849.40

構造登録者

Chen, Q.,Luo, M. (登録日: 2006-03-19, 公開日: 2007-04-03, 最終更新日: 2024-02-14)

主引用文献

Chen, Q.,You, D.,Liang, Y.,Su, X.,Gu, X.,Luo, M.,Zheng, X.
Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design.
Febs J., 274:4408-4415, 2007

PubMed Abstract: Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a potential target for structure-based inhibitor design for the treatment of parasitic diseases. We created point mutants of Thermoanaerobacter tengcongensis HGPRT and tested their activities to identify side chains that were important for function. Mutating residues Leu160 and Lys133 substantially diminished the activity of HGPRT, confirming their importance in catalysis. All 11 HGPRT mutants were subject to crystallization screening. The crystal structure of one mutant, L160I, was determined at 1.7 A resolution. Surprisingly, the active site is occupied by a peptide from the N-terminus of a neighboring tetramer. These crystal contacts suggest an alternate strategy for structure-based inhibitor design.

PubMed: 17662107
DOI: 10.1111/j.1742-4658.2007.05970.x

実験手法

X-RAY DIFFRACTION (1.7 Å)