GSBS Student Publications
Title
Crystallization of recombinant Leishmania major pteridine reductase 1 (PTR1)
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
1999-09-18
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Pharmacology and Molecular Toxicology
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The enzyme pteridine reductase (PTR1) has recently been discovered in the protozoan parasite Leishmania and validated as a target for therapeutic intervention. PTR1 is responsible for the salvage of pteridines and also contributes to antifolate drug resistance. Structural analysis, in combination with ongoing biochemical characterization will assist the elucidation of the structure-activity relationships of this important enzyme and support a structure-based approach to discover novel inhibitors. Recombinant L. major PTR1 has been purified from an Escherichia coli expression system and used in crystallization experiments. Orthorhombic crystals have been obtained and data to 2.8 A has been measured. The space group is P2(1)2(1)2 or P2(1)2(1)2(1) with unit-cell dimensions of a = 103.9, b = 134.7, c = 96.2 A. One homotetramer, of molecular mass approximately 120 kDa, probably constitutes the asymmetric unit and gives a Matthews coefficient, V(m), of 2.8 A(3) Da(-1) and 56% solvent volume. Self-rotation function calculations show a single well defined non-crystallographic twofold axis with features that might represent additional elements of non-crystallographic symmetry. The detail of exactly what constitutes the asymmetric unit will be resolved by structure determination.
DOI of Published Version
10.1107/S0907444999008999
Source
Acta Crystallogr D Biol Crystallogr. 1999 Sep;55(Pt 9):1608-10.
Journal/Book/Conference Title
Acta crystallographica. Section D, Biological crystallography
Related Resources
PubMed ID
10489462
Repository Citation
Gourley, David G.; Luba, James; Hardy, Larry W.; Beverley, Stephen M.; and Hunter, William N., "Crystallization of recombinant Leishmania major pteridine reductase 1 (PTR1)" (1999). GSBS Student Publications. 405.
https://escholarship.umassmed.edu/gsbs_sp/405