Drug Targets, Drug Effectors, and Drug Targeting and Delivery

Loiseau, Philippe M.; Barratt, Gillian

doi:10.1007/978-3-7091-1125-3_16

Cited by 1 publication

(1 citation statement)

References 172 publications

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“…This information also revealed that 64-447 amino acids make up the core domain sequence which comprises the active-cofactor binding site [8]. Leishmaniasis or Kala-azar is a neglected, major tropical vectorborne protozoan disease endemic in different parts of about 88 countries, where it is identified to have claimed the lives of approximately 350 million people [9][10][11][12]. The current status of available treatments for leishmaniasis is highly concerning as depicted by their lack of selectivity, adverse effects, toxicity, and persistent development of resistance [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Cystathionine β-Lyase-Like Protein with Pyridoxal Binding Domain Characterized in Leishmania major by Comparative Sequence Analysis and Homology Modelling

Negi

Gupta

Garg

et al. 2013

ISRN Computational Biology

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Cystathionine -lyase-like protein (CBLP), one of the key enzymes involved in methionine biosynthesis utilising pyridoxal phosphate (PLP) as a cofactor, has recently been reported in Leishmania major. Its presence in the parasite and absence in humans warrant its full characterisation and fruition as a potent, selective, and inevitable druggable target. Due to the unavailability of X-ray 3D structure of CBLP, a homology model for this protein was developed for the first time. The model was evaluated for PLP binding site and various conserve domain residues of the protein recommended by comparative sequence analyses by different protein analysis tools. The model was validated and discovered to be robust and statistically significant. The final model was superimposed on template of Arabidopsis thaliana (PDB ID: 1IBJ) and RMSD was found to be 0.486. The PLP binding site residues of both the proteins were ensued to be highly conserved indicated by Gly71, Met72, Tyr95, Asp169, and Ser193 as well as formation of aldimine bond with Lys194. This was further verified through molecular simulation of PLP into the cofactor binding site of the modelled protein.The present study may therefore play a directing role in the designing of novel, potential, and selective antileishmanial agents.

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