title: Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase.
abstract: Human cystathionine beta-synthase plays a key role in maintaining low intracellular levels of homocysteine and is unique in being a pyridoxal phosphate-dependent enzyme that is a hemeprotein. It catalyzes the beta-replacement of serine and homocysteine to generate the condensation product, cystathionine. While the structure of a truncated catalytic core of the protein has been determined by crystallography, a model for the full-length enzyme has been developed guided by hydrogen-deuterium exchange mass spectrometric and docking studies. In this review, we have utilized the available structural models for human cystathionine beta-synthase to conduct a structure-function analysis of a select group of pathogenic mutations described in patients with hereditary hyperhomocysteinemia.
authors.affiliation: Redox Biology Center and Department of Biological Chemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yamanishi
authors.forename: Omer
authors.initials: O
authors.lastname: Kabil
authors.forename: Suvajit
authors.initials: S
authors.lastname: Sen
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D002384:Catalysis; D003541:Cystathionine beta-Synthase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation
chemical_list: D006418:Heme; D003541:Cystathionine beta-Synthase