Acta parasitologica · 2023
Comparative Analysis of Leishmania major Nucleoside Hydrolases Toward Selecting Multi-target Strategy.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Farhadi Samaneh, Taghizadeh Mohammad, Mousavi-Niri Neda, Nemati Fahimeh
Аннотация
PURPOSE: Leishmania 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.
METHOD: In 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.
RESULTS: The 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.
CONCLUSION: Although, 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.
METHOD: In 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.
RESULTS: The 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.
CONCLUSION: Although, 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.