3UNW

Crystal Structure of Human GAC in Complex with Glutamate

3UNW の概要

• エントリーDOI: 10.2210/pdb3unw/pdb
• 関連するPDBエントリー: 3UO9
• 分子名称: Glutaminase kidney isoform, mitochondrial, GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: alpha/beta, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Cytoplasm, cytosol. Isoform 3: Mitochondrion: O94925
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 236340.48

構造登録者

DeLaBarre, B.,Gross, S.,Cheng, F.,Gao, Y.,Jha, A.,Jiang, F.,Song, J.J.,Wie, W.,Hurov, J. (登録日: 2011-11-16, 公開日: 2011-12-07, 最終更新日: 2024-02-28)

主引用文献

DeLaBarre, B.,Gross, S.,Fang, C.,Gao, Y.,Jha, A.,Jiang, F.,Song J, J.,Wei, W.,Hurov, J.B.
Full-length human glutaminase in complex with an allosteric inhibitor.
Biochemistry, 50:10764-10770, 2011

PubMed Abstract: Glutaminase (GLS1/2) catalyzes the conversion of L-glutamine to L-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido-1,2,4,thiadiazol-2-yl)ethyl sulfide (BPTES). We report here the first full-length crystal structure of GAC in the presence and absence of BPTES molecules. Two BPTES molecules bind at an interface region of the GAC tetramer in a manner that appears to lock the GAC tetramer into a nonproductive conformation. The importance of these loops with regard to overall enzymatic activity of the tetramer was revealed by a series of GAC point mutants designed to create a BPTES resistant GAC.

PubMed: 22049910
DOI: 10.1021/bi201613d

実験手法

X-RAY DIFFRACTION (2.56 Å)