| Literature DB >> 34417180 |
Patrick Rabe1, Jos J A G Kamps1,2,3, Kyle D Sutherlin4, James D S Linyard1, Pierre Aller2,3, Cindy C Pham4, Hiroki Makita4, Ian Clifton1, Michael A McDonough1, Thomas M Leissing1, Denis Shutin1, Pauline A Lang1, Agata Butryn2,3, Jürgen Brem1, Sheraz Gul4, Franklin D Fuller5, In-Sik Kim4, Mun Hon Cheah6, Thomas Fransson7, Asmit Bhowmick4, Iris D Young4,8, Lee O'Riordan4, Aaron S Brewster4, Ilaria Pettinati1, Margaret Doyle4, Yasumasa Joti9,10, Shigeki Owada9,10, Kensuke Tono9,10, Alexander Batyuk5, Mark S Hunter5, Roberto Alonso-Mori5, Uwe Bergmann11,12, Robin L Owen2, Nicholas K Sauter4, Timothy D W Claridge1, Carol V Robinson1, Vittal K Yachandra4, Junko Yano4, Jan F Kern13, Allen M Orville14,3, Christopher J Schofield15.
Abstract
Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.Entities:
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Year: 2021 PMID： 34417180 PMCID： PMC8378823 DOI： 10.1126/sciadv.abh0250
Source DB: PubMed Journal: Sci Adv ISSN： 2375-2548 Impact factor: 14.957