X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.

Autor:	Rabe P; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Kamps JJAG; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.; Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.; Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA, UK., Sutherlin KD; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Linyard JDS; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Aller P; Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.; Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA, UK., Pham CC; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Makita H; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Clifton I; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., McDonough MA; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Leissing TM; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Shutin D; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Lang PA; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Butryn A; Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.; Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA, UK., Brem J; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Gul S; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Fuller FD; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA., Kim IS; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Cheah MH; Department of Chemistry - Ångström, Molecular Biomimetics, Uppsala University, SE 751 20 Uppsala, Sweden., Fransson T; Interdisciplinary Center for Scientific Computing, University of Heidelberg, 69120 Heidelberg, Germany., Bhowmick A; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Young ID; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA., O'Riordan L; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Brewster AS; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Pettinati I; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Doyle M; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Joti Y; Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan.; RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan., Owada S; Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan.; RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan., Tono K; Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan.; RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan., Batyuk A; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA., Hunter MS; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA., Alonso-Mori R; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA., Bergmann U; Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.; Department of Physics, University of Wisconsin-Madison, 1150 University Avenue, Madison, WI 53706, USA., Owen RL; Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK., Sauter NK; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Claridge TDW; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Robinson CV; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK., Yachandra VK; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Yano J; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA., Kern JF; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. christopher.schofield@chem.ox.ac.uk allen.orville@diamond.ac.uk jfkern@lbl.gov., Orville AM; Diamond Light Source, Diamond House, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK. christopher.schofield@chem.ox.ac.uk allen.orville@diamond.ac.uk jfkern@lbl.gov.; Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA, UK., Schofield CJ; Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk allen.orville@diamond.ac.uk jfkern@lbl.gov.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Aug 20; Vol. 7 (34). Date of Electronic Publication: 2021 Aug 20 (Print Publication: 2021).
DOI:	10.1126/sciadv.abh0250
Abstrakt:	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. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze:	MEDLINE
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