Leishmania donovani pteridine reductase 1: Biochemical properties and structure-modeling studies

Kumar, Pranav ; Kumar, Ashutosh ; Verma, Shyam Sundar ; Dwivedi, Namrata ; Singh, Nasib ; Siddiqi, Mohammad Imran ; Tripathi, Rama Pati ; Dube, Anuradha ; Singh, Neeloo (2008) Leishmania donovani pteridine reductase 1: Biochemical properties and structure-modeling studies Experimental Parasitology, 120 (1). pp. 73-79. ISSN 0014-4894

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.exppara.2008.05.005

Abstract

Pteridine reductase 1 (PTR1, EC 1.5.1.33) is a NADPH dependent short-chain reductase (SDR) responsible for the salvage of pterins in the protozoan parasite Leishmania. This enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, therefore, for successful antifolate chemotherapy to be developed against Leishmania, it must target both enzyme activities. Based on homology model drawn on recombinant pteridine reductase isolated from a clinical isolate of L. donovani, we carried out molecular modeling and docking studies with two compounds of dihydrofolate reductase specificity showing promising antileishmanial activity in vitro. Both the inhibitors appeared to fit well in the active pocket revealing the tight binding of the carboxylic acid ethyl ester group of pyridine moiety to pteridine reductase and identify the important interactions necessary to assist the structure based development of novel pteridine reductase inhibitors.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
ID Code:101817
Deposited On:11 Mar 2017 15:05
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