Evidence map›Paper›PMID 38085461›Full record

ArticleActa parasitologica2024

Comparative Analysis of Leishmania major Nucleoside Hydrolases Toward Selecting Multi-target Strategy.

Samaneh Farhadi, Mohammad Taghizadeh, Neda Mousavi-Niri, Fahimeh Nemati

Abstract readComparative Study
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In one paragraph

Article in Acta parasitologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Samaneh FarhadiBiotechnology Department, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, 1916893813, Iran.ORCID http://orcid.org/0000-0002-3487-5679
Mohammad TaghizadehBiotechnology Department, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, 1916893813, Iran. mtaghizadeh@ut.ac.ir.ORCID http://orcid.org/0000-0002-8466-0887
Neda Mousavi-NiriBiotechnology Department, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, 1916893813, Iran.ORCID http://orcid.org/0000-0003-0914-1881
Fahimeh NematiBiotechnology Department, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, 1916893813, Iran.
Islamic Azad University Medical Branch of Tehran · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeLeishmania causes multiple types of leishmaniasis in different parts of the world. It has a lack of metabolic machine to produce purine bases. Therefore, the parasite produces purine bases through the breakdown of nutritional nucleotides and it makes the nucleoside hydrolases (NHs) good drug targets. They have different substrate-preferring (SP) types. Our objectives were modeling and comparative analysis of these protein structures for Leishmania major.

methodIn this work, available sequences for all SP types of L. major NH enzymes including inosine-uridine preferring NH (IUNH), inosine-guanosine preferring NH (IGNH), and inosine-adenosine-guanosine preferring NH (IAGNH) were used to make 24 structural models via SWISS-MODEL and LOMETS. After evaluating the structural models, three enzyme structures were finalized and used to analyze substrate-binding pockets.

resultsThe three SP types of L. major NH enzymes that can breakdown purine nucleosides were highly different in terms of sequence, structure, and profile of interacting residues within the substrate-binding pockets. In this study, new enzyme structures have been presented for three SP types and they have been compared in different aspects and it indicated that they were very different from each other.

conclusionAlthough, previously indicated that from these three SP types in genera other than Leishmania, the role of IGNH and IAGNH was greater than IUNH in supplying purine bases, till this work, just IUNH has been structurally studied and used in drug-design investigations for Leishmania. Therefore, we are offering to use all three SP types of NHs as multi-target strategy in anti-leishmaniosis drug-design studies.

Indexed as

Leishmania majorAmino Acid SequenceModels, MolecularN-Glycosyl HydrolasesProtozoan ProteinsSubstrate SpecificityN-Glycosyl HydrolasesProtozoan ProteinsCutaneous leishmaniasisLeishmania majorMulti-target strategyNucleoside hydrolasesProtein structural modelingSubstrate-preferring (substrate specificity)

Identifiers

PMID38085461
OpenAlexW4389624992

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