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  • The EMBO Journal (2001) 20, 3910 - 3916
  • doi:10.1093/emboj/20.15.3910

Structure of human cystathionine bold beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein

Markus Meier1, Miroslav Janosik2, Vladimir Kery2, Jan P. Kraus2 and Peter Burkhard1

  1. M.E.Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
  2. Departments of Pediatrics and Cellular and Structural Biology, University of Colorado School of Medicine, Denver, CO 80262, USA

Correspondence to:

Peter Burkhard, E-mail: Peter.Burkhard@unibas.ch

Received 20 April 2001; Accepted 8 June 2001; Revised 8 June 2001

Cystathionine beta-synthase (CBS) is a unique heme- containing enzyme that catalyzes a pyridoxal 5'-phosphate (PLP)-dependent condensation of serine and homocysteine to give cystathionine. Deficiency of CBS leads to homocystinuria, an inherited disease of sulfur metabolism characterized by increased levels of the toxic metabolite homocysteine. Here we present the X-ray crystal structure of a truncated form of the enzyme. CBS shares the same fold with O-acetylserine sulfhydrylase but it contains an additional N-terminal heme binding site. This heme binding motif together with a spatially adjacent oxidoreductase active site motif could explain the regulation of its enzyme activity by redox changes.

  • Keywords:

    • cystathionine beta-synthase,
    • cysteine biosynthesis,
    • heme protein,
    • pyridoxal 5'-phosphate,
    • X-ray crystal structure