HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mukherjee, T. Articles by Bhaduri, A. Search for Related Content PubMed PubMed Citation Articles by Mukherjee, T. Articles by Bhaduri, A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 263, Issue 2, 708-713, 01, 1988

Aspartate transcarbamylase from Leishmania donovani. A discrete, nonregulatory enzyme as a potential chemotherapeutic site

T Mukherjee, M Ray and A Bhaduri
Leishmania Group, Indian Institute of Chemical Biology 4, Calcutta.

Leishmania donovani is a protozoal pathogen that belongs to the kinetoplastida order. Unlike in other eucaryotic systems, the first three enzymes of the de novo pyrimidine biosynthetic pathway are not components of a multifunctional protein system. The three enzyme activities in the crude extract were separated on a Sephacryl S-200 column. Aspartate carbamoyltransferase (EC 2.1.3.2) has been purified to apparent homogeneity. The enzyme has an approximate molecular weight of 135,000 and seems to be a tetramer of equivalent subunits of molecular weight 35,000. The enzyme shows strictly hyperbolic kinetics with both the substrates under a variety of conditions and is not inhibited by nucleotide phosphates. Km for carbamyl phosphate is 3.1 x 10(-4) M and for aspartate is 7.6 x 10(-3) M. Apparently, the enzyme has no regulatory role in pyrimidine biosynthesis. N-(Phosphonoacetyl)- L-aspartic acid is a powerful competitive inhibitor (Ki = 5 x 10(-7) M) for this enzyme with carbamyl phosphate as substrate. This inhibitor completely inhibits the growth of the vector form of organism at 60 microM and significantly affects the growth of the pathogenic form in a macrophage assay system. The potency of the inhibitor is comparable with allopurinol which is undergoing human clinical trial as an antileishmanial drug.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. P. Burns, G. L. Mendz, and S. L. Hazell A Novel Mechanism for Resistance to the Antimetabolite N-Phosphonoacetyl-L-Aspartate by Helicobacter pylori J. Bacteriol., November 1, 1998; 180(21): 5574 - 5579. [Abstract] [Full Text]

				J. Hong, W. L. Salo, and P. M. Anderson Nucleotide Sequence and Tissue-specific Expression of the Multifunctional Protein Carbamoyl-phosphate Synthetase-Aspartate Transcarbamoylase-Dihydroorotase (CAD) mRNA in Squalus acanthias J. Biol. Chem., June 9, 1995; 270(23): 14130 - 14139. [Abstract] [Full Text] [PDF]