期刊
SCIENCE ADVANCES
卷 6, 期 14, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aay7919
关键词
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资金
- Indo-South Africa Joint Science and Technology Research Cooperation Grant - Department of Science and Technology, Government of India [DST/INT/SOUTH AFRICA/P-04/2014]
- National Research Foundation (NRF) of South Africa [90702]
- Department of Science and Technology (DST) of India [CRG/2019/001219]
- TIFR, India via the Department of Atomic Energy (DAE), Ramanujan Fellowship
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 similar to 25-angstrom 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.
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