Ferraroni Marta, Angeli Andrea, De Luca Viviana, Capasso Clemente, Supuran Claudiu T
Department of Chemistry "Ugo Schiff", University of Florence, Via Della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.
NEUROFARBA Department, University of Florence, 50019 Sesto Fiorentino, Florence, Italy.
J Struct Biol. 2025 Mar;217(1):108154. doi: 10.1016/j.jsb.2024.108154. Epub 2024 Dec 6.
Porphyromonas gingivalis, a key pathogen in periodontal, plays a critical role in systemic pathologiesdiseases by evading host defence mechanisms and invading periodontal tissues. Targeting its virulence mechanisms and overcoming drug resistance are essential steps toward effective therapeutic development. In this study, we focused on the Carbonic Anhydrase (CA, EC: 4.2.1.1) encoded by P. gingivalis as a potential drug target. We determined the crystal structure of PgiCA γ at a resolution of 2.4 Å and conducted kinetic characterization. The structure revealed that active PgiCA γ forms a trimer, with each monomer comprising a left-handed β-helix capped by a C-terminal α-helix and coordinated to a catalytic zinc ion through three histidine residues. Interestingly, one monomer displayed an atypical α-helix conformation, likely due to close interactions with neighbouring trimers within the crystal lattice (a probable crystallographic artefact). These findings provide new insights into the structural and functional properties of PgiCA γ, emphasizing its potential as a target for the development of novel anti-virulence therapies against P. gingivalis.
牙龈卟啉单胞菌是牙周炎的关键病原体，通过逃避宿主防御机制和侵入牙周组织，在全身性疾病中起关键作用。针对其毒力机制并克服耐药性是有效治疗开发的关键步骤。在本研究中，我们聚焦于牙龈卟啉单胞菌编码的碳酸酐酶（CA，EC：4.2.1.1）作为潜在药物靶点。我们以2.4 Å的分辨率测定了PgiCA γ的晶体结构并进行了动力学表征。该结构显示，活性PgiCA γ形成三聚体，每个单体包含由C端α螺旋封端的左手β螺旋，并通过三个组氨酸残基与催化锌离子配位。有趣的是，一个单体呈现出非典型的α螺旋构象，这可能是由于与晶格内相邻三聚体的紧密相互作用（可能是晶体学假象）。这些发现为PgiCA γ的结构和功能特性提供了新见解，强调了其作为开发针对牙龈卟啉单胞菌的新型抗毒力疗法靶点的潜力。
