6Y0P

isopenicillin N synthase in complex with IPN and Fe using FT-SSX methods

Summary for 6Y0P

• Entry DOI: 10.2210/pdb6y0p/pdb
• Related: 1BKO 1BLZ
• Descriptor: Isopenicillin N synthase, SULFATE ION, ISOPENICILLIN N, ... (5 entities in total)
• Functional Keywords: iron dependent dioxygenase, dna repair, oxidoreductase
• Biological source: Aspergillus nidulans FGSC A4
• Total number of polymer chains: 1
• Total formula weight: 38075.14

Authors

Rabe, P.,Beale, J.H.,Lang, P.A.,Dirr, A.S.,Leissing, T.M.,Butryn, A.,Aller, P.,Kamps, J.J.A.G.,Axford, D.,McDonough, M.A.,Orville, A.M.,Owen, R.,Schofield, C.J. (deposition date: 2020-02-10, release date: 2021-02-17, 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 (1.98 Å)