7Q4C
Local refinement structure of the C-domain of full-length, monomeric, soluble somatic angiotensin I-converting enzyme
7Q4C の概要
エントリーDOI | 10.2210/pdb7q4c/pdb |
関連するPDBエントリー | 7Q3Y 7Q4D 7Q4E |
EMDBエントリー | 13797 13799 13801 13802 13803 13804 |
分子名称 | Angiotensin-converting enzyme, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
機能のキーワード | zinc metalloprotease dicarboxypeptidase glycoprotein, hydrolase |
由来する生物種 | Homo sapiens (human) |
タンパク質・核酸の鎖数 | 1 |
化学式量合計 | 141689.35 |
構造登録者 | |
主引用文献 | Lubbe, L.,Sewell, B.T.,Woodward, J.D.,Sturrock, E.D. Cryo-EM reveals mechanisms of angiotensin I-converting enzyme allostery and dimerization. Embo J., 41:e110550-e110550, 2022 Cited by PubMed Abstract: 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. PubMed: 35818993DOI: 10.15252/embj.2021110550 主引用文献が同じPDBエントリー |
実験手法 | ELECTRON MICROSCOPY (4.08 Å) |
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