7R0S

Structure of a cytosolic sulfotransferase of Anopheles gambiae (AGAP001425) in complex with vanillin

Summary for 7R0S

• Entry DOI: 10.2210/pdb7r0s/pdb
• Descriptor: AGAP001425-PA, 4-hydroxy-3-methoxybenzaldehyde, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: anopheles gambiae, cytosolic sulfotransferase, sulfation, vanillin., transferase
• Biological source: Anopheles gambiae (African malaria mosquito)
• Total number of polymer chains: 2
• Total formula weight: 86199.50

Authors

Esposito Verza, A.,Miggiano, R.,Rizzi, R.,Rossi, F. (deposition date: 2022-02-02, release date: 2022-08-10, Last modification date: 2024-01-31)

Primary citation

Esposito Verza, A.,Miggiano, R.,Lombardo, F.,Fiorillo, C.,Arca, B.,Purghe, B.,Del Grosso, E.,Galli, U.,Rizzi, M.,Rossi, F.
Biochemical and structural analysis of a cytosolic sulfotransferase of the malaria vector Anopheles gambiae overexpressed in the reproductive tissues.
Curr Res Struct Biol, 4:246-255, 2022

PubMed Abstract: The temporary or permanent chemical modification of biomolecules is a crucial aspect in the physiology of all living species. However, while some modules are well characterised also in insects, others did not receive the same attention. This holds true for sulfo-conjugation that is catalysed by cytosolic sulfotransferases (SULT), a central component of the metabolism of endogenous low molecular weight molecules and xenobiotics. In particular, limited information is available about the functional roles of the mosquito predicted enzymes annotated as SULTs in genomic databases. The herein described research is the first example of a biochemical and structural study of a SULT of a mosquito species, in general, and of the malaria vector in particular. We confirmed that the AGAP001425 transcript displays a peculiar expression pattern that is suggestive of a possible involvement in modulating the mosquito reproductive tissues physiology, a fact that could raise attention on the enzyme as a potential target for insect-containment strategies. The crystal structures of the enzyme in alternative ligand-bound states revealed elements distinguishing SULT-001425 from other characterized SULTs, including a peculiar conformational plasticity of a discrete region that shields the catalytic cleft and that could play a main role in the dynamics of the reaction and in the substrate selectivity of the enzyme. Along with further biochemical studies, our structural investigations could provide a framework for the discovery of small-molecule inhibitors to assess the effect of interfering with SULT-001425-mediated catalysis at the organismal level.

PubMed: 35941867
DOI: 10.1016/j.crstbi.2022.07.001

Experimental method

X-RAY DIFFRACTION (2.1 Å)