Crystallization and preliminary crystallographic characterization of LmACR2, an arsenate/antimonate reductase from Leishmania major.

Abstract

Arsenic is present in the biosphere owing either to the presence of pesticides and herbicides used in agricultural and industrial activities or to leaching from geological formations. The health effects of prolonged exposure to arsenic can be devastating and may lead to various forms of cancer. Antimony(V), which is chemically very similar to arsenic, is used instead in the treatment of leishmaniasis, an infection caused by the protozoan parasite Leishmania sp.; the reduction of pentavalent antimony contained in the drug Pentostam to the active trivalent form arises from the presence in the Leishmania genome of a gene, LmACR2, coding for the protein LmACR2 (14.5 kDa, 127 amino acids) that displays weak but significant sequence similarity to the catalytic domain of Cdc25 phosphatase and to rhodanese enzymes. For structural characterization, LmACR2 was overexpressed, purified to homogeneity and crystallized in a trigonal space group (P321 or P3(1)21/P3(2)21). The protein crystallized in two distinct trigonal crystal forms, with unit-cell parameters a = b = 111.0, c = 86.1 A and a = b = 111.0, c = 175.6 A, respectively. At a synchrotron beamline, the diffraction pattern extended to a resolution limit of 1.99 A.

• Authors: Davide Bisacchi, Yao Zhou, Barry P Rosen, Rita Mukhopadhyay, Domenico Bordo
• Journal: Acta crystallographica. Section F, Structural biology and crystallization communications (Acta Crystallogr Sect F Struct Biol Cryst Commun) Vol. 62 Issue Pt 10 Pg. 976-9 (Oct 01 2006) ISSN: 1744-3091 [Electronic] England
• PMID: 17012788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ion Pumps
• Multienzyme Complexes
• Antimony
• Arsenite Transporting ATPases

Topics

• Amino Acid Sequence
• Animals
• Antimony (chemistry, metabolism)
• Arsenite Transporting ATPases
• Cloning, Molecular
• Crystallization
• Crystallography, X-Ray
• Ion Pumps (chemistry, genetics, isolation & purification)
• Leishmania major (chemistry, enzymology)
• Molecular Sequence Data
• Multienzyme Complexes (chemistry, genetics, isolation & purification)
• Sequence Alignment