title: A distal pocket Leu residue inhibits the binding of O2 and NO at the distal heme site of cytochrome c'.
abstract: Cytochromes c' are pentacoordinate heme proteins with sterically hindered distal sites that bind NO and CO but do not form stable complexes with O(2). Removal of distal pocket steric hindrance via a Leu→Ala mutation yields favorable O(2) binding (K(d) ~49 nM) without apparent H-bond stabilization of the Fe-O(2) moiety, as well as an extremely high distal heme-NO affinity (K(d) ~70 fM). The native Leu residue inhibits distal coordination of diatomic ligands by decreasing k(on) as well as increasing k(off). The connection between distal steric constraints, k(off) values, and distal to proximal heme-NO conversion is discussed.
authors.affiliation: Department of Chemistry and Biochemistry, Eastern Oregon University, La Grande, Oregon 97850, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Garton
authors.forename: David A
authors.initials: DA
authors.lastname: Pixton
authors.forename: Christine A
authors.initials: CA
authors.lastname: Petersen
authors.forename: Robert R
authors.initials: RR
authors.lastname: Eady
authors.forename: S Samar
authors.initials: SS
authors.lastname: Hasnain
authors.forename: Colin R
authors.initials: CR
authors.lastname: Andrew
mesh_terms: D000421:Alcaligenes / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D045304:Cytochromes c / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D017354:Point Mutation
chemical_list: D009569:Nitric Oxide; D006418:Heme; D045304:Cytochromes c; D007930:Leucine; D010100:Oxygen