6JT8

Crystal structure of 450-451_deletion mutant of FGAM Synthetase

Summary for 6JT8

• Entry DOI: 10.2210/pdb6jt8/pdb
• Descriptor: Phosphoribosylformylglycinamidine synthase, 1,2-ETHANEDIOL, ADENOSINE-5'-DIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: fgam synthetase, biosynthetic protein
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 1
• Total formula weight: 146925.94

Authors

Sharma, N.,Ahalawat, N.,Sandhu, P.,Mondal, J.,Anand, R. (deposition date: 2019-04-10, release date: 2020-03-04, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)