• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Mol Biochem Parasitol 2006 Feb;145(2):147-57

Cloning and characterization of angiotensin converting enzyme related dipeptidylcarboxypeptidase from Leishmania donovani.

Goyal N, Duncan R, Selvapandiyan A, Debrabant A, Baig MS, Nakhasi HL

Goyal N, Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA


We report the first identification, gene cloning, recombinant expression and biochemical characterization of an angiotensin converting enzyme (ACE) related dipeptidylcarboxypeptidase (DCP) in a protozoan parasite. The mammalian counterpart of this enzyme, peptidyl dipeptidase A (a carboxyl dipeptidase) also known as ACE leads to the cleavage of angiotensin I to produce a potent vasopressor. The catalytic enzyme activity of its Escherichia coli DCP counter part can be inhibited by the antihypertensive drug captopril, suggesting that this class of enzymes constitutes a novel target for drugs and vaccines. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding a DCP enzyme for the kinetoplast protozoan Leishmania donovani (LdDCP) that was differentially expressed in promastigote and amastigote stages of the parasite life cycle. Both RNA and protein levels of LdDCP are higher in axenic amastigotes compared to promastigotes. Immuno-fluorescence analysis revealed the cytosolic expression of the protein. Primary structure analysis of LdDCP revealed the presence of an active Zn binding site. When expressed in E. coli, the recombinant enzyme showed carboxy-dipeptidase activity with synthetic substrates. Replacement of two histidine and one glutamic acid at positions 466, 470 and 467, respectively, with alanine residues in its active site resulted in loss of enzyme activity. Captopril, an ACE specific inhibitor was able both to reduce significantly LdDCP enzyme activity and to inhibit promastigote growth. Both its cytosolic location and close homology to DCPs from bacterial species suggests a role in parasite nutrition. Further, identification of LdDCP now provides an opportunity to investigate Leishmania peptidases for their potential as drug and vaccine targets.

Category: Journal Article
PubMed ID: #16257064
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29