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-Structure paper
タイトル | Cryo-EM reveals mechanisms of angiotensin I-converting enzyme allostery and dimerization. |
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ジャーナル・号・ページ | EMBO J, Vol. 41, Issue 16, Page e110550, Year 2022 |
掲載日 | 2022年7月12日 |
著者 | Lizelle Lubbe / Bryan Trevor Sewell / Jeremy D Woodward / Edward D Sturrock / |
PubMed 要旨 | Hypertension (high blood pressure) is a major risk factor for cardiovascular disease, which is the leading cause of death worldwide. The somatic isoform of angiotensin I-converting enzyme (sACE) ...Hypertension (high blood pressure) is a major risk factor for cardiovascular disease, which is the leading cause of death worldwide. The somatic isoform of angiotensin I-converting enzyme (sACE) plays a critical role in blood pressure regulation, and ACE inhibitors are thus widely used to treat hypertension and cardiovascular disease. Our current understanding of sACE structure, dynamics, function, and inhibition has been limited because truncated, minimally glycosylated forms of sACE are typically used for X-ray crystallography and molecular dynamics simulations. Here, we report the first cryo-EM structures of full-length, glycosylated, soluble sACE (sACE ). Both monomeric and dimeric forms of the highly flexible apo enzyme were reconstructed from a single dataset. The N- and C-terminal domains of monomeric sACE were resolved at 3.7 and 4.1 Å, respectively, while the interacting N-terminal domains responsible for dimer formation were resolved at 3.8 Å. Mechanisms are proposed for intradomain hinging, cooperativity, and homodimerization. Furthermore, the observation that both domains were in the open conformation has implications for the design of sACE modulators. |
リンク | EMBO J / PubMed:35818993 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.63 - 4.34 Å |
構造データ | EMDB-13797, PDB-7q3y: EMDB-13799, PDB-7q49: EMDB-13801, PDB-7q4c: EMDB-13802: Structure of full-length, dimeric, soluble somatic angiotensin I-converting enzyme EMDB-13803, PDB-7q4d: EMDB-13804, PDB-7q4e: |
化合物 | ChemComp-ZN: ChemComp-CL: ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | HYDROLASE / Zinc metalloprotease Dicarboxypeptidase Glycoprotein |