Publication

Article Metrics

Citations


Online attention

A Distal Pocket Leu Residue Inhibits the Binding of O2 and NO at the Distal Heme Site of Cytochrome C

DOI: 10.1021/ja209770p DOI Help

Authors: Elizabeth M. Garton (Department of Chemistry and Biochemistry, Eastern Oregon University, La Grande, Oregon 97850, United States) , David A. Pixton (Department of Chemistry and Biochemistry, Eastern Oregon University, La Grande, Oregon 97850, United States) , Christine A. Petersen (Department of Chemistry and Biochemistry, Eastern Oregon University, La Grande, Oregon 97850, United States) , Robert R. Eady (Molecular Biophysics Group, Faculty of Health and Life Sciences, Institute of Integrative Biology, University of Liverpool) , S. Samar Hasnain (Molecular Biophysics Group, Faculty of Health and Life Sciences, Institute of Integrative Biology, University of Liverpool) , Colin R. Andrew (Department of Chemistry and Biochemistry, Eastern Oregon University, La Grande, Oregon 97850, United States)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society , VOL 134 (3) , PAGES 1461 - 1463

State: Published (Approved)
Published: January 2012
Diamond Proposal Number(s): 7044

Abstract: Cytochromes C are pentacoordinate heme proteins with sterically hindered distal sites that bind NO and CO but do not form stable complexes with O2. Removal of distal pocket steric hindrance via a Leu to Ala mutation yields favorable O2 binding (Kd 49 nM) without apparent H-bond stabilization of the Fe┬ľO2 moiety, as well as an extremely high distal heme-NO affinity (Kd 70 fM). The native Leu residue inhibits distal coordination of diatomic ligands by decreasing kon as well as increasing koff. The connection between distal steric constraints, koff values, and distal to proximal heme-NO conversion is discussed.

Subject Areas: Biology and Bio-materials, Chemistry, Environment


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography