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Article

Exploration of the Binding Site of Arachidonic Acid in gp63 of Leishmania mexicana and in Orthologous Proteins in Clinically Important Parasites

by
Verónica Ivonne Hernández-Ramírez
1,
Audifás-Salvador Matus-Meza
2,
Norma Oviedo
3,
Marco Antonio Magos-Castro
4,
Carlos Osorio-Trujillo
1,
Lizbeth Salazar-Villatoro
1,
Luis Alejandro Constantino-Jonapa
5 and
Patricia Talamás-Rohana
1,*
1
Departamento de Infectómica y Patogénesis Molecular, CINVESTAV, Av. IPN No. 2508, Col. San Pedro Zacatenco, México City 07360, Mexico
2
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 69198, USA
3
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional La Raza, IMSS, Av. Jacarandas S/N, La Raza, Azcapotzalco, México City 02990, Mexico
4
Departamento de Genética y Biología Molecular, CINVESTAV, Av. IPN No. 2508, Col. San Pedro Zacatenco, México City 07360, Mexico
5
Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, UNAM, Instituto Nacional de Cardiología Ignacio Chávez, México City 14080, Mexico
*
Author to whom correspondence should be addressed.
Pathogens 2024, 13(9), 718; https://doi.org/10.3390/pathogens13090718
Submission received: 26 July 2024 / Revised: 13 August 2024 / Accepted: 20 August 2024 / Published: 25 August 2024
(This article belongs to the Special Issue Parasite Infection and Tropical Infectious Diseases)

Abstract

Recently, we published that the monoclonal antibody (D12 mAb) recognizes gp63 of L. mexicana, and it is responsible for COX activity. This D12 mAb exhibited cross-reactivity with Trypanosoma cruzi, Entamoeba histolytica, Acanthamoeba castellanii, and Naegleria fowleri. COX activity assays performed in these parasites suggested the potential presence of such enzymatic activity. In our investigation, we confirmed that wild-type recombinant gp63 exhibits COX-like activity, in contrast to a mutated recombinant gp63 variant. Consequently, our objective was to identify sequences orthologous to gp63 and subsequently analyze the binding of arachidonic acid (AA) to the putative active sites of these proteins. Given the absence of a crystallized structure for this protein in the Protein Data Bank (PDB), it was imperative to first obtain a three-dimensional structure by homology modeling, using leishmanolysin from Leishmania major (PDB ID: LML1) as a template in the Swiss model database. The results obtained through molecular docking simulations revealed the primary interactions of AA close to the Zinc atom present in the catalytic site of gp63-like molecules of several parasites, predominantly mediated by hydrogen bonds with HIS264, HIS268 and HIS334. Furthermore, COX activity was evaluated in commensal species such as E. dispar and during the encystment process of E. invadens.
Keywords: Acanthamoeba castellanii; COX-like activity; Entamoeba spp.; Leishmania mexicana gp63; Naegleria fowleri; Trypanosoma cruzi; orthologous proteins to gp63 Acanthamoeba castellanii; COX-like activity; Entamoeba spp.; Leishmania mexicana gp63; Naegleria fowleri; Trypanosoma cruzi; orthologous proteins to gp63
Graphical Abstract

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MDPI and ACS Style

Hernández-Ramírez, V.I.; Matus-Meza, A.-S.; Oviedo, N.; Magos-Castro, M.A.; Osorio-Trujillo, C.; Salazar-Villatoro, L.; Constantino-Jonapa, L.A.; Talamás-Rohana, P. Exploration of the Binding Site of Arachidonic Acid in gp63 of Leishmania mexicana and in Orthologous Proteins in Clinically Important Parasites. Pathogens 2024, 13, 718. https://doi.org/10.3390/pathogens13090718

AMA Style

Hernández-Ramírez VI, Matus-Meza A-S, Oviedo N, Magos-Castro MA, Osorio-Trujillo C, Salazar-Villatoro L, Constantino-Jonapa LA, Talamás-Rohana P. Exploration of the Binding Site of Arachidonic Acid in gp63 of Leishmania mexicana and in Orthologous Proteins in Clinically Important Parasites. Pathogens. 2024; 13(9):718. https://doi.org/10.3390/pathogens13090718

Chicago/Turabian Style

Hernández-Ramírez, Verónica Ivonne, Audifás-Salvador Matus-Meza, Norma Oviedo, Marco Antonio Magos-Castro, Carlos Osorio-Trujillo, Lizbeth Salazar-Villatoro, Luis Alejandro Constantino-Jonapa, and Patricia Talamás-Rohana. 2024. "Exploration of the Binding Site of Arachidonic Acid in gp63 of Leishmania mexicana and in Orthologous Proteins in Clinically Important Parasites" Pathogens 13, no. 9: 718. https://doi.org/10.3390/pathogens13090718

APA Style

Hernández-Ramírez, V. I., Matus-Meza, A.-S., Oviedo, N., Magos-Castro, M. A., Osorio-Trujillo, C., Salazar-Villatoro, L., Constantino-Jonapa, L. A., & Talamás-Rohana, P. (2024). Exploration of the Binding Site of Arachidonic Acid in gp63 of Leishmania mexicana and in Orthologous Proteins in Clinically Important Parasites. Pathogens, 13(9), 718. https://doi.org/10.3390/pathogens13090718

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