Crystallization and preliminary X-ray diffraction of malate dehydrogenase from Plasmodium falciparum

Author(s)

Wrenger, Carsten ; Mueller, Ingrid B. ; Butzloff, Sabine ; Jordanova, Rositsa ; Lunev, Sergey ; Groves, Matthew R.

• Document type: Journal article
• Source: ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS; v. 68, p. 4-pg., 2012-06-01.

Abstract

The expression, purification, crystallization and preliminary X-ray diffraction characterization of malate dehydrogenase (MDH) from the malarial parasite Plasmodium falciparum (PfMDH) are reported. In order to gain a deeper understanding of the function and role of PfMDH, the protein was purified to homogeneity. The purified protein crystallized in space group P1, with unit-cell parameters a = 72, b = 157, c = 159 angstrom, a = 105, beta = 101, ? = 95 degrees. The resulting crystals diffracted to a maximal resolution of 2.24 angstrom and the structure has been solved by molecular replacement, with 16 monomers in the asymmetric unit. The 16 monomers are arranged into four independent tetramers, in agreement with previous reports demonstrating the tetrameric solution state of PfMDH. The X-ray structure of PfMDH is expected to clarify the differences in catalysis by PfMDH compared with other MDH family members and to provide a basis for the structure-based design of specific PfMDH inhibitors as well as general MDH inhibitors. (AU)

• FAPESP's process: 09/54325-2 - Elucidation of vitamin B metabolism in the human malaria parasite Plasmodium falciparum and their validation as a target for chemotherapy
• Grantee: Carsten Wrenger
• Support Opportunities: Research Grants - Young Investigators Grants