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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of full-length, monomeric, soluble somatic angiotensin I-converting enzyme showing the N- and C-terminal ellipsoid domains | |||||||||
![]() | Globally-sharpened map of full-length monomeric somatic angiotensin I-converting enzyme showing N-terminal and C-terminal ellipsoid domains | |||||||||
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機能・相同性 | ![]() mononuclear cell proliferation / cell proliferation in bone marrow / bradykinin receptor binding / regulation of angiotensin metabolic process / exopeptidase activity / substance P catabolic process / peptidyl-dipeptidase A / tripeptidyl-peptidase activity / regulation of renal output by angiotensin / negative regulation of calcium ion import ...mononuclear cell proliferation / cell proliferation in bone marrow / bradykinin receptor binding / regulation of angiotensin metabolic process / exopeptidase activity / substance P catabolic process / peptidyl-dipeptidase A / tripeptidyl-peptidase activity / regulation of renal output by angiotensin / negative regulation of calcium ion import / positive regulation of peptidyl-cysteine S-nitrosylation / response to laminar fluid shear stress / negative regulation of gap junction assembly / metallodipeptidase activity / positive regulation of systemic arterial blood pressure / cellular response to aldosterone / hormone catabolic process / bradykinin catabolic process / angiogenesis involved in coronary vascular morphogenesis / response to thyroid hormone / antigen processing and presentation of peptide antigen via MHC class I / negative regulation of glucose import / vasoconstriction / hormone metabolic process / neutrophil mediated immunity / regulation of smooth muscle cell migration / regulation of hematopoietic stem cell proliferation / mitogen-activated protein kinase binding / embryo development ending in birth or egg hatching / chloride ion binding / mitogen-activated protein kinase kinase binding / positive regulation of neurogenesis / arachidonic acid secretion / post-transcriptional regulation of gene expression / eating behavior / heterocyclic compound binding / lung alveolus development / heart contraction / peptide catabolic process / response to dexamethasone / regulation of heart rate by cardiac conduction / regulation of systemic arterial blood pressure by renin-angiotensin / regulation of vasoconstriction / peptidyl-dipeptidase activity / hematopoietic stem cell differentiation / blood vessel remodeling / angiotensin maturation / amyloid-beta metabolic process / animal organ regeneration / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / positive regulation of vasoconstriction / sperm midpiece / blood vessel diameter maintenance / response to nutrient levels / basal plasma membrane / kidney development / angiotensin-activated signaling pathway / female pregnancy / cellular response to glucose stimulus / brush border membrane / regulation of synaptic plasticity / metalloendopeptidase activity / regulation of blood pressure / metallopeptidase activity / male gonad development / peptidase activity / actin binding / spermatogenesis / endopeptidase activity / response to lipopolysaccharide / lysosome / calmodulin binding / response to hypoxia / endosome / response to xenobiotic stimulus / positive regulation of apoptotic process / external side of plasma membrane / negative regulation of gene expression / proteolysis / extracellular space / zinc ion binding / extracellular exosome / extracellular region / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.34 Å | |||||||||
![]() | Lubbe L / Sewell BT / Sturrock ED | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM reveals mechanisms of angiotensin I-converting enzyme allostery and dimerization. 著者: Lizelle Lubbe / Bryan Trevor Sewell / Jeremy D Woodward / Edward D Sturrock / ![]() 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. | |||||||||
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 59.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 26.4 KB 26.4 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 8.9 KB | 表示 | ![]() |
画像 | ![]() | 59.9 KB | ||
マスクデータ | ![]() ![]() | 64 MB 64 MB | ![]() | |
その他 | ![]() ![]() ![]() | 59.4 MB 59.4 MB 59.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 740.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 739.9 KB | 表示 | |
XML形式データ | ![]() | 16.3 KB | 表示 | |
CIF形式データ | ![]() | 20.8 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7q3yMC ![]() 7q49C ![]() 7q4cC ![]() 7q4dC ![]() 7q4eC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
電子顕微鏡画像生データ | ![]() Data size: 3.8 TB Data #1: Unaligned multi-frame cryo-EM micrographs of human somatic angiotensin I-converting enzyme in the apo state [micrographs - multiframe]) |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | Globally-sharpened map of full-length monomeric somatic angiotensin I-converting enzyme showing N-terminal and C-terminal ellipsoid domains | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
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投影像・断面図 |
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密度ヒストグラム |
-マスク #2
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密度ヒストグラム |
-追加マップ: Raw, unfiltered full map of full-length monomeric somatic...
ファイル | emd_13797_additional_1.map | ||||||||||||
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注釈 | Raw, unfiltered full map of full-length monomeric somatic angiotensin I-converting enzyme | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Raw, unfiltered half-map B of full-length monomeric somatic...
ファイル | emd_13797_half_map_1.map | ||||||||||||
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注釈 | Raw, unfiltered half-map B of full-length monomeric somatic angiotensin I-converting enzyme | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Raw, unfiltered half-map A of full-length monomeric somatic...
ファイル | emd_13797_half_map_2.map | ||||||||||||
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注釈 | Raw, unfiltered half-map A of full-length monomeric somatic angiotensin I-converting enzyme | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : full-length, soluble, monomeric somatic angiotensin I-converting ...
全体 | 名称: full-length, soluble, monomeric somatic angiotensin I-converting enzyme |
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要素 |
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-超分子 #1: full-length, soluble, monomeric somatic angiotensin I-converting ...
超分子 | 名称: full-length, soluble, monomeric somatic angiotensin I-converting enzyme タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() ![]() 組換プラスミド: pcDNA3.1+ |
分子量 | 理論値: 139 KDa |
-分子 #1: Angiotensin-converting enzyme
分子 | 名称: Angiotensin-converting enzyme / タイプ: protein_or_peptide / ID: 1 詳細: Soluble secreted form of human somatic angiotensin I-converting enzyme terminating at Ser1211 コピー数: 1 / 光学異性体: LEVO EC番号: 加水分解酵素; 糖加水分解酵素; 配糖体結合加水分解酵素または糖加水分解酵素 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 139.614 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: LDPGLQPGNF SADEAGAQLF AQSYNSSAEQ VLFQSVAASW AHDTNITAEN ARRQEEAALL SQEFAEAWGQ KAKELYEPIW QNFTDPQLR RIIGAVRTLG SANLPLAKRQ QYNALLSNMS RIYSTAKVCL PNKTATCWSL DPDLTNILAS SRSYAMLLFA W EGWHNAAG ...文字列: LDPGLQPGNF SADEAGAQLF AQSYNSSAEQ VLFQSVAASW AHDTNITAEN ARRQEEAALL SQEFAEAWGQ KAKELYEPIW QNFTDPQLR RIIGAVRTLG SANLPLAKRQ QYNALLSNMS RIYSTAKVCL PNKTATCWSL DPDLTNILAS SRSYAMLLFA W EGWHNAAG IPLKPLYEDF TALSNEAYKQ DGFTDTGAYW RSWYNSPTFE DDLEHLYQQL EPLYLNLHAF VRRALHRRYG DR YINLRGP IPAHLLGDMW AQSWENIYDM VVPFPDKPNL DVTSTMLQQG WNATHMFRVA EEFFTSLELS PMPPEFWEGS MLE KPADGR EVVCHASAWD FYNRKDFRIK QCTRVTMDQL STVHHEMGHI QYYLQYKDLP VSLRRGANPG FHEAIGDVLA LSVS TPEHL HKIGLLDRVT NDTESDINYL LKMALEKIAF LPFGYLVDQW RWGVFSGRTP PSRYNFDWWY LRTKYQGICP PVTRN ETHF DAGAKFHVPN VTPYIRYFVS FVLQFQFHEA LCKEAGYEGP LHQCDIYRST KAGAKLRKVL QAGSSRPWQE VLKDMV GLD ALDAQPLLKY FQLVTQWLQE QNQQNGEVLG WPEYQWHPPL PDNYPEGIDL VTDEAEASKF VEEYDRTSQV VWNEYAE AN WNYNTNITTE TSKILLQKNM QIANHTLKYG TQARKFDVNQ LQNTTIKRII KKVQDLERAA LPAQELEEYN KILLDMET T YSVATVCHPN GSCLQLEPDL TNVMATSRKY EDLLWAWEGW RDKAGRAILQ FYPKYVELIN QAARLNGYVD AGDSWRSMY ETPSLEQDLE RLFQELQPLY LNLHAYVRRA LHRHYGAQHI NLEGPIPAHL LGNMWAQTWS NIYDLVVPFP SAPSMDTTEA MLKQGWTPR RMFKEADDFF TSLGLLPVPP EFWNKSMLEK PTDGREVVCH ASAWDFYNGK DFRIKQCTTV NLEDLVVAHH E MGHIQYFM QYKDLPVALR EGANPGFHEA IGDVLALSVS TPKHLHSLNL LSSEGGSDEH DINFLMKMAL DKIAFIPFSY LV DQWRWRV FDGSITKENY NQEWWSLRLK YQGLCPPVPR TQGDFDPGAK FHIPSSVPYI RYFVSFIIQF QFHEALCQAA GHT GPLHKC DIYQSKEAGQ RLATAMKLGF SRPWPEAMQL ITGQPNMSAS AMLSYFKPLL DWLRTENELH GEKLGWPQYN WTPN SARSE GPLPDS |
-分子 #7: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 7 / コピー数: 1 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #8: CHLORIDE ION
分子 | 名称: CHLORIDE ION / タイプ: ligand / ID: 8 / コピー数: 1 / 式: CL |
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分子量 | 理論値: 35.453 Da |
-分子 #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 9 / コピー数: 4 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #10: water
分子 | 名称: water / タイプ: ligand / ID: 10 / コピー数: 1 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1.5 mg/mL | ||||||||||||
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緩衝液 | pH: 7.5 構成要素:
詳細: Solutions were prepared with deionized water | ||||||||||||
グリッド | モデル: Quantifoil R2/2 / 材質: COPPER / メッシュ: 200 / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV 詳細: Diluted protein (in buffer containing zinc chloride and sodium chloride) was incubated on ice for 30 minutes after which it was applied to the grid, incubated for 30 seconds, and blotted for ...詳細: Diluted protein (in buffer containing zinc chloride and sodium chloride) was incubated on ice for 30 minutes after which it was applied to the grid, incubated for 30 seconds, and blotted for 3 seconds before plunging. | ||||||||||||
詳細 | The protein was stored at 3.0mg/ml in 50mM HEPES (pH 7.5) and diluted immediately prior to grid preparation |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / デジタル化 - サイズ - 横: 5760 pixel / デジタル化 - サイズ - 縦: 4092 pixel / 撮影したグリッド数: 1 / 実像数: 11628 / 平均露光時間: 3.0 sec. / 平均電子線量: 43.0 e/Å2 詳細: Images were recorded in super-resolution mode with 40 frames per image |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.8 µm / 倍率(公称値): 81000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT / 当てはまり具合の基準: Correlation coefficient |
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得られたモデル | ![]() PDB-7q3y: |