Structural insights into mutations of cystathionine β-synthase

• Published in: Biochimica et biophysica acta Vol. 1647; no. 1; pp. 206 - 213
• Main Authors: Meier, Markus, Oliveriusova, Jana, Kraus, Jan P., Burkhard, Peter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 11.04.2003
• Subjects: Binding Sites; Cystathionine beta-Synthase - chemistry; Cystathionine beta-Synthase - genetics; Cystathionine β-synthase; Dimerization; Heme - chemistry; Heme protein; Homocysteine; Homocystinuria - genetics; Humans; Mutation; Pyridoxal 5′-phosphate; X-ray crystal structure; Heme protein; X-ray crystal structure; Pyridoxal 5′-phosphate; Cystathionine β-synthase; Mutation; Homocysteine
• ISSN: 1570-9639; 0006-3002; 1878-1454
• DOI: 10.1016/S1570-9639(03)00048-7

Cystathionine β-synthase (CBS) is a unique heme-containing enzyme that catalyses 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 amino acid metabolism characterised by increased levels of homocysteine and methionine and decreased levels of cysteine. Presently, more than 100 CBS mutations have been described which lead to homocystinuria with different degrees of severity in the patients. We have recently solved the crystal structure of a truncated form of this enzyme, which enables us to correlate some of these mutations with the structure.