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Yorodumi- PDB-1r4l: Inhibitor Bound Human Angiotensin Converting Enzyme-Related Carbo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1r4l | ||||||
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Title | Inhibitor Bound Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2) | ||||||
Components |
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Keywords | HYDROLASE / zinc metallopeptidase domain / collectrin homology domain / inhibitor bound conformation / chloride ion binding site / zinc ion binding site | ||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of inflammatory response / regulation of cell population proliferation / endopeptidase activity / Potential therapeutics for SARS / Induction of Cell-Cell Fusion / entry receptor-mediated virion attachment to host cell / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / receptor-mediated virion attachment to host cell / apical plasma membrane / symbiont entry into host cell / membrane raft / endoplasmic reticulum lumen / cell surface / extracellular space / zinc ion binding / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å | ||||||
Authors | Towler, P. / Staker, B. / Prasad, S.G. / Menon, S. / Ryan, D. / Tang, J. / Parsons, T. / Fisher, M. / Williams, D. / Dales, N.A. ...Towler, P. / Staker, B. / Prasad, S.G. / Menon, S. / Ryan, D. / Tang, J. / Parsons, T. / Fisher, M. / Williams, D. / Dales, N.A. / Patane, M.A. / Pantoliano, M.W. | ||||||
Citation | Journal: J.Biol.Chem. / Year: 2004 Title: ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. Authors: Towler, P. / Staker, B. / Prasad, S.G. / Menon, S. / Tang, J. / Parsons, T. / Ryan, D. / Fisher, M. / Williams, D. / Dales, N.A. / Patane, M.A. / Pantoliano, M.W. #1: Journal: J.Am.Chem.Soc. / Year: 2002 Title: Substrate Based Design of the First Class of Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Inhibitors Authors: Dales, N. / Gould, A.E. / Brown, J.A. / Calderwood, E.F. / Guan, B. / Minor, C.A. / Gavin, J.M. / Hales, P. / Kaushik, V.K. / Stewart, M. / Tummino, P.J. / Vickers, C.S. / Ocain, T.D. / Patane, M.A. #2: Journal: J.Biol.Chem. / Year: 2002 Title: Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase Authors: Vickers, C. / Hales, P. / Kaushik, V. / Dick, L. / Gavin, J. / Tang, J. / Godbout, K. / Parsons, T. / Baronas, E. / Hsieh, F. / Acton, S. / Patane, M. / Nichols, A. / Tummino, P. | ||||||
History |
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Remark 999 | SEQUENCE The complete sequence crystallized by the authors (residues 1-740 of reference sequence GB ...SEQUENCE The complete sequence crystallized by the authors (residues 1-740 of reference sequence GB 11225609) is as follows: MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNY NTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQ QNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIM ANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYW RGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPS YISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQ RIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDF RILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEI MSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEK WRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSND YSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWS PYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQ MILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRIN DAFRLNDNSLEFLGIQPTLGPPNQPPVS The electron density map for much of the collectrin homology domain (residues 616-740) is weak. Only about half of this domain was visible in the electron density map, and what can be seen is ambiguous due to topology and connectivity issues. For this reason, residues beginning at 901 are labeled as unknown (UNK). Each segment of unknown residues has been assigned a unique chain ID. However, it should be understood that only one sequence (residues 1-740) was crystallized. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1r4l.cif.gz | 146.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1r4l.ent.gz | 113 KB | Display | PDB format |
PDBx/mmJSON format | 1r4l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1r4l_validation.pdf.gz | 854.6 KB | Display | wwPDB validaton report |
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Full document | 1r4l_full_validation.pdf.gz | 914.2 KB | Display | |
Data in XML | 1r4l_validation.xml.gz | 31.7 KB | Display | |
Data in CIF | 1r4l_validation.cif.gz | 43.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r4/1r4l ftp://data.pdbj.org/pub/pdb/validation_reports/r4/1r4l | HTTPS FTP |
-Related structure data
Related structure data | 1r42SC S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Disordered segment of collectrin homology ... , 4 types, 4 molecules BCDE
#2: Protein/peptide | Mass: 528.644 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) |
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#3: Protein/peptide | Mass: 1720.111 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) |
#4: Protein/peptide | Mass: 1549.902 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) |
#5: Protein/peptide | Mass: 1209.482 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) |
-Protein / Sugars , 2 types, 3 molecules A
#1: Protein | Mass: 70999.820 Da / Num. of mol.: 1 / Fragment: Extracellular domains Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACE2 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9BYF1 |
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#6: Sugar |
-Non-polymers , 4 types, 16 molecules
#7: Chemical | ChemComp-CL / |
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#8: Chemical | ChemComp-ZN / |
#9: Chemical | ChemComp-XX5 / ( |
#10: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.94 Å3/Da / Density % sol: 58.18 % | |||||||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 19% PEG 3000, 100mM Tris-HCl, 600mM NaCl, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K | |||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS Temperature: 16-18 ℃ / Method: vapor diffusion, hanging drop | |||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction source | Source: SYNCHROTRON / Site: NSLS / Beamline: X25 |
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Detector | Detector: AREA DETECTOR |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
Reflection | Resolution: 3→50 Å / Num. obs: 17526 / % possible obs: 95.9 % / Observed criterion σ(I): 0 / Biso Wilson estimate: 63 Å2 / Rsym value: 0.07 / Net I/σ(I): 13.2 |
Reflection shell | Resolution: 3→3.08 Å / Mean I/σ(I) obs: 2 / Rsym value: 0.23 / % possible all: 74.5 |
Reflection | *PLUS Highest resolution: 3 Å / Lowest resolution: 43.3 Å / Num. obs: 17228 / % possible obs: 96.8 % / Rmerge(I) obs: 0.07 |
Reflection shell | *PLUS Highest resolution: 3 Å / Lowest resolution: 3.19 Å / % possible obs: 85.1 % / Num. unique obs: 2250 / Rmerge(I) obs: 0.204 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1R42 Resolution: 3→43.26 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 2938880.39 / Data cutoff high rms absF: 2938880.39 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 56.626 Å2 / ksol: 0.304373 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 74.5 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 3→43.26 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3→3.19 Å / Rfactor Rfree error: 0.029 / Total num. of bins used: 6
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Xplor file |
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Refinement | *PLUS Highest resolution: 3 Å / Lowest resolution: 43.3 Å / Num. reflection Rfree: 1723 | ||||||||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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LS refinement shell | *PLUS Rfactor Rfree: 0.46 |