title: Crystallization and preliminary X-ray analysis of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae.
abstract: 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 mM ammonium sulfate in 100 mM 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 A resolution. The crystals are shown to be orthorhombic and have been assigned to space group P2(1)2(1)2, with unit-cell parameters a = 95.88, b = 112.58, c = 90.40 A and a scaling Rsym 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Madabushi
authors.forename: Sibani
authors.initials: S
authors.lastname: Chakraborty
authors.forename: S Zoë
authors.initials: SZ
authors.lastname: Fisher
authors.forename: José C
authors.initials: JC
authors.lastname: Clemente
authors.forename: Charles
authors.initials: C
authors.lastname: Yowell
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
authors.forename: John B
authors.initials: JB
authors.lastname: Dame
authors.forename: Ben M
authors.initials: BM
authors.lastname: Dunn
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010965:Plasmodium malariae / Q000201:enzymology*; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
chemical_list: D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin