A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes.
- 5 July 1994
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (14) , 6614-6618
- https://doi.org/10.1073/pnas.91.14.6614
Abstract
Human cystathionine beta-synthase (CBS; EC 4.2.1.22) deficiency results in a recessive genetic disorder whose clinical and biochemical manifestations vary greatly among affected individuals. In an effort to identify and analyze mutations in the human CBS gene, we have developed a yeast expression system for human CBS. We have cloned and sequenced a human cDNA that codes for CBS and have expressed the human CBS protein in yeast cells lacking endogenous CBS. The human enzyme produced in yeast is functional both in vitro and in vivo. We have also cloned and sequenced the yeast gene, CYS4, that codes for CBS. The predicted human and yeast CBS proteins are 38% identical and 72% similar to each other, as well as sharing significant similarity with bacterial cysteine synthase. These results demonstrate the evolutionary conservation of CBS and establish the utility of a yeast expression system for studying human CBS.Keywords
This publication has 27 references indexed in Scilit:
- Human cystathionine β-synthase cDNA: sequence, alternative splicing and expression in cultured cellsHuman Molecular Genetics, 1993
- Screening for mutations by expressing patient cDNA segments inE. coli: Homocystinuria due to cystathionine β-synthase deficiencyHuman Mutation, 1992
- Hyperhomocysteinemia: An Independent Risk Factor for Vascular DiseaseNew England Journal of Medicine, 1991
- A functional interaction between the C-terminal domain of RNA polymerase II and the negative regulator SIN1Cell, 1991
- Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: Paradigm of Pitfalls in phenotypesAmerican Journal of Medical Genetics, 1990
- Heterozygosity for Homocystinuria in Premature Peripheral and Cerebral Occlusive Arterial DiseaseNew England Journal of Medicine, 1985
- Moderate homocysteinemia--a possible risk factor for arteriosclerotic cerebrovascular disease.Stroke, 1984
- A positive selection for mutants lacking orotidine-5′-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistanceMolecular Genetics and Genomics, 1984
- Enzyme studies in cystathionine‐β‐synthase deficiency: A possible effect of elevated intracellular levels of homocystine in kinetic studiesJournal of Inherited Metabolic Disease, 1978
- HomocystinuriaJournal of Clinical Investigation, 1978