9BPL

Crystal structure of Adenylosuccinate Lyase from Leishmania major

Summary for 9BPL

• Entry DOI: 10.2210/pdb9bpl/pdb
• Descriptor: Adenylosuccinate lyase, GLYCEROL, SULFATE ION, ... (7 entities in total)
• Functional Keywords: adenylossucinate lyase, asl, leishmania major, lyase
• Biological source: Leishmania major
• Total number of polymer chains: 2
• Total formula weight: 108421.59

Authors

Rosa e Silva, I.,Mantovani, M.,Nagem, R.,Cardona, A.,Reboredo, E.,Thiemann, O. (deposition date: 2024-05-07, release date: 2025-10-08, Last modification date: 2026-06-17)

Primary citation

E Silva, I.R.,Mantovani, M.,Lino, M.E.S.D.,Albuquerque, A.O.,da Silva, J.H.M.,Nagem, R.A.P.,Rojas, A.L.,Sartori, G.R.,Horjales, E.,Campbell, D.,Thiemann, O.H.
Structural Insights Into the Function of Leishmania major Adenylosuccinate Lyase.
Proteins, 2026

PubMed Abstract: One of several intriguing aspects of kinetoplastid biochemistry is the complete dependence on host purines and purine recycling due to the lack of a de novo purine biosynthesis pathway. Adenylosuccinate lyase (ASL, EC 4.3.2.2) is a key enzyme in the purine synthesis pathway responsible for the conversion of adenylosuccinate into adenosine monophosphate (AMP), representing a potential target for an effective drug design against leishmaniasis. Here, we report the in vitro kinetics studies and the crystal structure of the Leishmania major Friedlin adenylosuccinate lyase (LmASL). Furthermore, we characterize allosteric communication networks within the protein. We propose a phenylpiperazine derivative, itraconazole, as a promising candidate for selective interaction with the LmASL substrate-binding site by molecular docking and molecular dynamics simulations. Finally, we expand the current understanding on trypanosomatid ASL by demonstrating its requirement for the normal growth of Trypanosoma brucei procyclic form. Our data will substantiate future studies aimed at developing an effective and specific treatment against leishmaniasis.

PubMed: 42260760
DOI: 10.1002/prot.70150

Experimental method

X-RAY DIFFRACTION (1.97 Å)