Molecular characterization of the ldmdr1 multidrug resistance gene from Leishmania donovani.
The ldmdr1 gene that confers resistance to multiple structurally dissimilar hydrophobic drugs in Leishmania donovani has been isolated within a 5.4-kb XmaI fragment from a genomic library of L. donovani DNA and its protein coding region sequenced. The longest open reading frame within ldmdr1 encodes a 146.5-kDa protein of 1341 amino acids, designated LDMDR1. The primary structure and predicted membrane topology of LDMDR1 indicates that it is a member of the P-glycoprotein superfamily with the greatest homology to the mammalian multidrug resistance P-glycoproteins. A 2.3-kb SalI fragment derived from a second ldmdr1 allele was also cloned from the L. donovani library. Nucleotide sequence analysis of a portion of the SalI insert revealed 5 single base differences from its counterpart within the 5.4-kb XmaI fragment, one of which created a PvuI restriction site polymorphism. Southern blots of PvuI-digested DNA divulged that the amplified ldmdr1 gene copies in a multidrug-resistant L. donovani strain were all derived from the single ldmdr1 allele whose protein coding segment was sequenced in its entirety.
Hendrickson
N
N
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098.
Sifri
C D
CD
Henderson
D M
DM
Allen
T
T
Wirth
D F
DF
Ullman
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D005784:Gene Amplification; D017125:Genes, Protozoan; D007893:Leishmania donovani / Q000187:drug effects / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D016054:DNA, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins