PRIMARY STRUCTURE AND EXPRESSION OF THE DIHYDROPTEROATE SYNTHETASE GENE OF PLASMODIUM-FALCIPARUM
- Author(s)
- Triglia, T; Cowman, AF;
- Details
- Publication Year 1994-07-19,Volume 91,Issue #15,Page 7149-7153
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The enzyme dihydropteroate synthetase (DHPS) from Plasmodium falciparum is involved in the mechanism of action of the sulfone/sulfonamide group of drugs. We describe the cloning and sequencing of the gene encoding the P. falciparum DHPS enzyme and show that it is a bifunctional enzyme that includes dihydro-6-hydroxymethylpterin pyrophosphokinase (PPPK) at the N terminus of DHPS. The gene encodes a putative protein of 83 kDa that contains two domains that are homologous with the DHPS and PPPK enzymes of other organisms. The PPPK-DHPS gene is encoded on chromosome 8 and has two introns. An antibody raised to the PPPK region of the protein was found to recognize a 68-kDa protein that is expressed throughout the asexual life cycle of the parasite. We have determined the sequence of the DHPS portion of the gene from sulfadoxine-sensitive and -resistant P. falciparum clones and identified sequence differences that may have a role in sulfone/sulfonamide resistance.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- SYNTHESIS FAS GENE; SYNTHASE GENE; HYDROXYMETHYLDIHYDROPTERIN PYROPHOSPHOKINASE; STREPTOCOCCUS-PNEUMONIAE; SULFONAMIDE RESISTANCE; ESCHERICHIA-COLI; DNA-SEQUENCE; ACID; DIHYDROFOLATE; BIOSYNTHESIS
- Publisher's Version
- https://doi.org/10.1073/pnas.91.15.7149
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-07-19 12:00:00