Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase.
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.
Yamanishi
Mamoru
M
Redox Biology Center and Department of Biological Chemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
Kabil
Omer
O
Sen
Suvajit
S
Banerjee
Ruma
R
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
D006418:Heme; D003541:Cystathionine beta-Synthase