Computational Characterization of Reaction Intermediates in the Photocycle of the Sensory Domain of the AppA Blue Light Photoreceptor†

2010 ◽  
Vol 87 (3) ◽  
pp. 564-573 ◽  
Author(s):  
Maria G. Khrenova ◽  
Tatiana Domratcheva ◽  
Ilme Schlichting ◽  
Bella L. Grigorenko ◽  
Alexander V. Nemukhin
Keyword(s):  
Blue Light ◽  
Reaction Intermediates ◽  
Blue Light Photoreceptor

Genetic and molecular characterization of a blue light photoreceptor MGWC-1 in Magnaporth oryzae

2011 ◽  
Vol 48 (4) ◽  
pp. 400-407 ◽  
Author(s):  
Soonok Kim ◽  
Pratibha Singh ◽  
Jaejin Park ◽  
Sohyun Park ◽  
Aaron Friedman ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Blue Light ◽  
Blue Light Photoreceptor

scholarly journals Unveiling the crucial intermediates in androgen production

2015 ◽  
Vol 112 (52) ◽  
pp. 15856-15861 ◽  
Author(s):  
Piotr J. Mak ◽  
Michael C. Gregory ◽  
Ilia G. Denisov ◽  
Stephen G. Sligar ◽  
James R. Kincaid
Keyword(s):  
Bond Cleavage ◽  
Nucleophilic Attack ◽  
Reaction Intermediates ◽  
Structural Determinants ◽  
Initial Product ◽  
Androgen Synthesis ◽  
Ferric Peroxo ◽  
Enzymatic Mechanisms ◽  
Primary Substrate

Ablation of androgen production through surgery is one strategy against prostate cancer, with the current focus placed on pharmaceutical intervention to restrict androgen synthesis selectively, an endeavor that could benefit from the enhanced understanding of enzymatic mechanisms that derives from characterization of key reaction intermediates. The multifunctional cytochrome P450 17A1 (CYP17A1) first catalyzes the typical hydroxylation of its primary substrate, pregnenolone (PREG) and then also orchestrates a remarkable C17–C20 bond cleavage (lyase) reaction, converting the 17-hydroxypregnenolone initial product to dehydroepiandrosterone, a process representing the first committed step in the biosynthesis of androgens. Now, we report the capture and structural characterization of intermediates produced during this lyase step: an initial peroxo-anion intermediate, poised for nucleophilic attack on the C20 position by a substrate-associated H-bond, and the crucial ferric peroxo-hemiacetal intermediate that precedes carbon–carbon (C-C) bond cleavage. These studies provide a rare glimpse at the actual structural determinants of a chemical transformation that carries profound physiological consequences.

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