6ZAQ

Room temperature XFEL Isopenicillin N synthase structure in complex with Fe and IPN after dioxygen exposure

Summary for 6ZAQ

• Entry DOI: 10.2210/pdb6zaq/pdb
• Related: 1BLZ 1QJE
• Descriptor: Isopenicillin N synthase, FE (II) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: isopenicillin n synthase, oxygen binding, xfel, time-resolved crystallography, oxidoreductase
• Biological source: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
• Total number of polymer chains: 1
• Total formula weight: 38075.14

Authors

Rabe, P.,Kamps, J.J.A.G.,Sutherlin, K.,Pharm, C.,McDonough, M.A.,Leissing, T.M.,Aller, P.,Butryn, A.,Linyard, J.,Lang, P.,Brem, J.,Fuller, F.D.,Batyuk, A.,Hunter, M.S.,Pettinati, I.,Clifton, I.J.,Alonso-Mori, R.,Gul, S.,Young, I.,Kim, I.,Bhowmick, A.,ORiordan, L.,Brewster, A.S.,Claridge, T.D.W.,Sauter, N.K.,Yachandra, V.,Yano, J.,Kern, J.F.,Orville, A.M.,Schofield, C.J. (deposition date: 2020-06-05, release date: 2021-06-09, Last modification date: 2024-01-24)

Primary citation

Rabe, P.,Kamps, J.J.A.G.,Sutherlin, K.D.,Linyard, J.D.S.,Aller, P.,Pham, C.C.,Makita, H.,Clifton, I.,McDonough, M.A.,Leissing, T.M.,Shutin, D.,Lang, P.A.,Butryn, A.,Brem, J.,Gul, S.,Fuller, F.D.,Kim, I.S.,Cheah, M.H.,Fransson, T.,Bhowmick, A.,Young, I.D.,O'Riordan, L.,Brewster, A.S.,Pettinati, I.,Doyle, M.,Joti, Y.,Owada, S.,Tono, K.,Batyuk, A.,Hunter, M.S.,Alonso-Mori, R.,Bergmann, U.,Owen, R.L.,Sauter, N.K.,Claridge, T.D.W.,Robinson, C.V.,Yachandra, V.K.,Yano, J.,Kern, J.F.,Orville, A.M.,Schofield, C.J.
X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.
Sci Adv, 7:-, 2021

PubMed Abstract: Isopenicillin synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin (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.

PubMed: 34417180
DOI: 10.1126/sciadv.abh0250

Experimental method

X-RAY DIFFRACTION (1.6 Å)