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-Structure paper
タイトル | Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 5979, Year 2022 |
掲載日 | 2022年10月10日 |
著者 | Xiaoyun Yang / Zongqiang Li / Liang Zhao / Zhun She / Zengqiang Gao / Sen-Fang Sui / Yuhui Dong / Yanhua Li / |
PubMed 要旨 | PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids-the main component of cell membranes-and assists the invasion of the opportunistic ...PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids-the main component of cell membranes-and assists the invasion of the opportunistic pathogen Pseudomonas aeruginosa. As a cognate immunity protein, PA3488 can inhibit the activity of PldA to avoid self-toxicity. However, the precise inhibitory mechanism remains elusive. We determine the crystal structures of full-length and truncated PldA and the cryogenic electron microscopy structure of the PldA-PA3488 complex. Structural analysis reveals that there are different intermediates of PldA between the "open" and "closed" states of the catalytic pocket, accompanied by significant conformational changes in the "lid" region and the peripheral helical domain. Through structure-based mutational analysis, we identify the key residues responsible for the enzymatic activity of PldA. Together, these data provide an insight into the molecular mechanisms of PldA invasion and its neutralization by PA3488, aiding future design of PLD-targeted inhibitors and drugs. |
リンク | Nat Commun / PubMed:36216841 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.1 - 3.05 Å |
構造データ | EMDB-32438, PDB-7wdk: PDB-7v53: PDB-7v55: |
化合物 | ChemComp-HOH: ChemComp-CA: |
由来 |
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キーワード | HYDROLASE / phospholipase D / Toxin / IMMUNE SYSTEM / PldA / PA3488 / Complex |