Structure of a Substrate Complex of Mammalian Cytochrome P450 2C5 at 2.3 Å Resolution:  Evidence for Multiple Substrate Binding Modes†,‡

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6370-6379 ◽  
Author(s):  
Michael R. Wester ◽  
Eric F. Johnson ◽  
Cristina Marques-Soares ◽  
Patrick M. Dansette ◽  
Daniel Mansuy ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Binding Modes ◽  
Substrate Complex ◽  
Multiple Substrate

scholarly journals Multiple substrate-binding sites are retained in cytochrome P450 3A4 mutants with decreased cooperativity

Xenobiotica ◽  
2010 ◽  
Vol 41 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Harshica Fernando ◽  
Jessica A. O. Rumfeldt ◽  
Nadezhda Y. Davydova ◽  
James R. Halpert ◽  
Dmitri R. Davydov
Keyword(s):  
Cytochrome P450 ◽  
Binding Sites ◽  
Substrate Binding ◽  
Cytochrome P450 3A4 ◽  
Multiple Substrate ◽  
Substrate Binding Sites

scholarly journals QM/MM Study of the Active Species of the Human Cytochrome P450 3A4, and the Influence Thereof of the Multiple Substrate Binding

2007 ◽  
Vol 111 (49) ◽  
pp. 13822-13832 ◽  
Author(s):  
Dan Fishelovitch ◽  
Carina Hazan ◽  
Hajime Hirao ◽  
Haim J. Wolfson ◽  
Ruth Nussinov ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Active Species ◽  
Cytochrome P450 3A4 ◽  
Human Cytochrome ◽  
Multiple Substrate

Pyrene·Pyrene Complexes at the Active Site of Cytochrome P450 3A4:  Evidence for a Multiple Substrate Binding Site

2002 ◽  
Vol 124 (40) ◽  
pp. 11866-11867 ◽  
Author(s):  
Michael J. Dabrowski ◽  
Michael L. Schrag ◽  
Larry C. Wienkers ◽  
William M. Atkins
Keyword(s):  
Cytochrome P450 ◽  
Binding Site ◽  
Active Site ◽  
Substrate Binding ◽  
Cytochrome P450 3A4 ◽  
Substrate Binding Site ◽  
Multiple Substrate

Multiple Substrate Binding by Cytochrome P450 3A4: Estimation of the Number of Bound Substrate Molecules

2008 ◽  
Vol 36 (10) ◽  
pp. 2136-2144 ◽  
Author(s):  
Yury Kapelyukh ◽  
Mark J. I. Paine ◽  
Jean-Didier Maréchal ◽  
Michael J. Sutcliffe ◽  
C. Roland Wolf ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Cytochrome P450 3A4 ◽  
Multiple Substrate

Role of Cytochrome P450 in Tulip Bulb Probed by Substrate-Binding Studies

1992 ◽  
Vol 36 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Steven L. Kelly ◽  
Aysegul Topal ◽  
Ian Barnett ◽  
Diane E. Kelly ◽  
George A. F. Hendry
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Binding Studies ◽  
Tulip Bulb

scholarly journals Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Mor Goldfeder ◽  
Margarita Kanteev ◽  
Sivan Isaschar-Ovdat ◽  
Noam Adir ◽  
Ayelet Fishman
Keyword(s):  
Substrate Binding ◽  
Copper Proteins ◽  
Binding Modes ◽  
Type 3

scholarly journals Structural insights into oxidation of medium-chain fatty acids and flavanone by myxobacterial cytochrome P450 CYP267B1

2018 ◽  
Vol 475 (17) ◽  
pp. 2801-2817 ◽  
Author(s):  
Ilona K. Jóźwik ◽  
Martin Litzenburger ◽  
Yogan Khatri ◽  
Alexander Schifrin ◽  
Marco Girhard ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cytochrome P450 ◽  
Saturated Fatty Acids ◽  
Decanoic Acid ◽  
Dodecanoic Acid ◽  
Binding Modes ◽  
Cytochrome P450 Enzymes ◽  
Tetradecanoic Acid ◽  
Medium Chain ◽  
Pharmaceutical Industries

Oxidative biocatalytic reactions performed by cytochrome P450 enzymes (P450s) are of high interest for the chemical and pharmaceutical industries. CYP267B1 is a P450 enzyme from myxobacterium Sorangium cellulosum So ce56 displaying a broad substrate scope. In this work, a search for new substrates was performed, combined with product characterization and a structural analysis of substrate-bound complexes using X-ray crystallography and computational docking. The results demonstrate the ability of CYP267B1 to perform in-chain hydroxylations of medium-chain saturated fatty acids (decanoic acid, dodecanoic acid and tetradecanoic acid) and a regioselective hydroxylation of flavanone. The fatty acids are mono-hydroxylated at different in-chain positions, with decanoic acid displaying the highest regioselectivity towards ω-3 hydroxylation. Flavanone is preferably oxidized to 3-hydroxyflavanone. High-resolution crystal structures of CYP267B1 revealed a very spacious active site pocket, similarly to other P450s capable of converting macrocyclic compounds. The pocket becomes more constricted near to the heme and is closed off from solvent by residues of the F and G helices and the B–C loop. The crystal structure of the tetradecanoic acid-bound complex displays the fatty acid bound near to the heme, but in a nonproductive conformation. Molecular docking allowed modeling of the productive binding modes for the four investigated fatty acids and flavanone, as well as of two substrates identified in a previous study (diclofenac and ibuprofen), explaining the observed product profiles. The obtained structures of CYP267B1 thus serve as a valuable prediction tool for substrate hydroxylations by this highly versatile enzyme and will encourage future selectivity changes by rational protein engineering.

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