Open AccessCrystallization and preliminary X‐ray analysis of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae
Author(s) -
Madabushi Amrita,
Chakraborty Sibani,
Fisher S. Zoë,
Clemente José C.,
Yowell Charles,
AgbandjeMcKenna Mavis,
Dame John B.,
Dunn Ben M.,
McKenna Robert
Publication year - 2005
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309105001405
Subject(s) - plasmodium malariae , ammonium sulfate , orthorhombic crystal system , plasmodium falciparum , crystallization , eimeria , crystallography , chemistry , biology , crystal structure , malaria , plasmodium vivax , microbiology and biotechnology , chromatography , immunology , organic chemistry
Plasmepsin 4 from the malarial parasite Plasmodium malariae (PmPM4) is a member of the plasmepsins ( Plasmodium pepsins), a subfamily of the pepsin‐like aspartic proteases whose ortholog in the malarial parasite P. falciparum is involved in hemoglobin digestion in its digestive vacuole. Crystals of PmPM4 in complex with the small‐molecule inhibitor AG1776 have been grown from a precipitant of 15% PEG 4000 and 200 m M ammonium sulfate in 100 m M sodium acetate pH 4.5. X‐ray diffraction data were collected on a Rigaku rotating‐anode generator from a single crystal under cryoconditions, with a maximal useful diffraction pattern to 3.3 Å resolution. The crystals are shown to be orthorhombic and have been assigned to space group P 2 1 2 1 2, with unit‐cell parameters a = 95.88, b = 112.58, c = 90.40 Å and a scaling R sym of 0.104 for 14 334 unique reflections. Packing consideration and self‐rotation function results indicate that there are two molecules per asymmetric unit. It is expected that in the near future the structure of PmPM4 will be obtained using molecular‐replacement methods, obtaining phases from previously determined plasmepsin structures. Elucidation of the structure of PmPM4 in complex with inhibitors may be paramount to producing new antimalarial therapeutic agents.