title: Oligomeric status of human cystathionine beta-synthase modulates AdoMet binding.
abstract: Cystathionine beta-synthase (CBS) plays a key role in the metabolism of sulfur-containing amino acids. CBS is a multidomain tetrameric enzyme allosterically activated by S-adenosylmethionine (AdoMet). Recent crystallographic analyses of engineered CBS lacking the loop made up of residues 516-525 revealed discrepancies in AdoMet binding compared to previous biophysical studies on a full-length CBS. Here, we show that removal of the loop 516-525 functionally eliminates the high affinity sites responsible for kinetic stabilization of the full-length enzyme and yields a dimeric AdoMet-inducible enzyme, in which kinetic stabilization is now exerted by AdoMet binding to the remaining low affinity sites.
authors.affiliation: Department of Physical Chemistry, Faculty of Sciences, University of Granada, Spain.
authors.forename: Angel L
authors.initials: AL
authors.lastname: Pey
authors.affiliation: Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC bioGUNE), Derio, Spain.
authors.forename: Luis Alfonso
authors.initials: LA
authors.lastname: Martínez-Cruz
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Kraus
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Majtan
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D003541:Cystathionine beta-Synthase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004795:Enzyme Stability; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009154:Mutation; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011993:Recombinant Fusion Proteins; D012436:S-Adenosylmethionine; D003541:Cystathionine beta-Synthase
keywords: S-adenosylmethionine; calorimetry; cystathionine beta-synthase; oligomerization