title: Modulation of cystathionine beta-synthase activity by the Arg-51 and Arg-224 mutations.
abstract: Human cystathionine beta-synthase (CBS) catalyzes a pyridoxal 5'-phosphate (PLP) dependent beta-replacement reaction to synthesize cystathionine from serine and homocysteine. The enzyme is unique in bearing not only a catalytically important PLP but also heme. In order to study a regulatory process mediated by heme, we performed mutagenesis of Arg-51 and Arg-224, which have hydrogen-bonding interactions with propionate side chains of the prosthetic group. It was found that the arginine mutations decrease CBS activity by approximately 50%. The results indicate that structural changes in the heme vicinity are transmitted to PLP existing 20 A away from heme. A possible explanation of our results is discussed on the basis of CBS structure.
authors.affiliation: Department of Biological Sciences, Yamaguchi University, Yamaguchi, Japan. ozakis@yamaguchi-u.ac.jp
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sada
mesh_terms: D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002384:Catalysis; D003540:Cystathionine / Q000235:genetics; D003541:Cystathionine beta-Synthase / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011732:Pyridoxal Phosphate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D003540:Cystathionine; D006418:Heme; D011732:Pyridoxal Phosphate; D003541:Cystathionine beta-Synthase; D000409:Alanine