Accession Number:

ADA331561

Title:

Crystallation, X-Ray Structure Determination and Structure-Based Drug Design for Targeted Malarial Enzymes

Descriptive Note:

Annual rept. 15 Jun 96-14 Jun 97,

Corporate Author:

ALABAMA UNIV IN BIRMINGHAM

Personal Author(s):

• DeLucas, Lawrence J.

Report Date:

1997-07-01

Pagination or Media Count:

40.0

Abstract:

The aim of this project is to identify specific inhibitors of some enzymes of malaria parasite. Inhibitors will be designed based on the high-resolution crystal structure of individual target enzymes. We have already determined the crystal structure of P. falciparum lactate dehydrogenase, a key enzyme in the glycolytic pathway, to high resolution. This structure is currently being used for designing lead inhibitors. We have also purified PFPK-DHPS bifunctional enzyme for structure analysis and are presently screening for crystallization conditions. We have also optimized the purification of P. falciparum cyclophilin. We have also crystallized P. falciparum Rab6 for structure determination. This is the first Rab protein of the malaria parasite to be crystallized.

Descriptors:

• *PARASITES
• *MALARIA
• *MOSQUITO BORNE DISEASES
• CRYSTAL STRUCTURE
• ENZYMES
• STRUCTURAL ANALYSIS
• CRYSTALLIZATION
• X RAYS
• PURIFICATION
• HUMAN BODY
• INHIBITORS
• PLASMODIUM FALCIPARUM
• MORTALITY RATE
• VACCINES
• MORBIDITY
• CHEMOTHERAPEUTIC AGENTS
• LACTIC DEHYDROGENASE

Subject Categories:

• Medicine and Medical Research
• Microbiology
• Crystallography

Distribution Statement:

APPROVED FOR PUBLIC RELEASE