6JT7

Crystal structure of 452-453_deletion mutant of FGAM Synthetase

6JT7 の概要

• エントリーDOI: 10.2210/pdb6jt7/pdb
• 分子名称: Phosphoribosylformylglycinamidine synthase, 1,2-ETHANEDIOL, IMIDAZOLE, ... (9 entities in total)
• 機能のキーワード: fgam synthetase, biosynthetic protein
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 150137.11

構造登録者

Sharma, N.,Ahalawat, N.,Sandhu, P.,Mondal, J.,Anand, R. (登録日: 2019-04-10, 公開日: 2020-03-04, 最終更新日: 2023-11-22)

主引用文献

Sharma, N.,Ahalawat, N.,Sandhu, P.,Strauss, E.,Mondal, J.,Anand, R.
Role of allosteric switches and adaptor domains in long-distance cross-talk and transient tunnel formation.
Sci Adv, 6:eaay7919-eaay7919, 2020

PubMed Abstract: Transient tunnels that assemble and disassemble to facilitate passage of unstable intermediates in enzymes containing multiple reaction centers are controlled by allosteric cues. Using the 140-kDa purine biosynthetic enzyme PurL as a model system and a combination of biochemical and x-ray crystallographic studies, we show that long-distance communication between ~25-Å distal active sites is initiated by an allosteric switch, residing in a conserved catalytic loop, adjacent to the synthetase active site. Further, combinatory experiments seeded from molecular dynamics simulations help to delineate transient states that bring out the central role of nonfunctional adaptor domains. We show that carefully orchestrated conformational changes, facilitated by interplay of dynamic interactions at the allosteric switch and adaptor-domain interface, control reactivity and concomitant formation of the ammonia tunnel. This study asserts that substrate channeling is modulated by allosteric hotspots that alter protein energy landscape, thereby allowing the protein to adopt transient conformations paramount to function.

PubMed: 32284973
DOI: 10.1126/sciadv.aay7919

実験手法

X-RAY DIFFRACTION (1.86 Å)