+Open data
-Basic information
Entry | Database: PDB / ID: 4az3 | |||||||||
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Title | crystal structure of cathepsin a, complexed with 15a | |||||||||
Components | (LYSOSOMAL PROTECTIVE PROTEIN ...) x 2 | |||||||||
Keywords | HYDROLASE / DRUG DISCOVERY / CARBOXYPEPTIDASE / CARDIOVASCULAR | |||||||||
Function / homology | Function and homology information carboxypeptidase C / Defective NEU1 causes sialidosis / serine-type carboxypeptidase activity / Sialic acid metabolism / regulation of chaperone-mediated autophagy / Glycosphingolipid catabolism / negative regulation of chaperone-mediated autophagy / carboxypeptidase activity / enzyme activator activity / MHC class II antigen presentation ...carboxypeptidase C / Defective NEU1 causes sialidosis / serine-type carboxypeptidase activity / Sialic acid metabolism / regulation of chaperone-mediated autophagy / Glycosphingolipid catabolism / negative regulation of chaperone-mediated autophagy / carboxypeptidase activity / enzyme activator activity / MHC class II antigen presentation / lysosomal lumen / intracellular protein transport / regulation of protein stability / azurophil granule lumen / lysosome / intracellular membrane-bounded organelle / Neutrophil degranulation / endoplasmic reticulum / proteolysis / extracellular exosome / extracellular region / membrane Similarity search - Function | |||||||||
Biological species | HOMO SAPIENS (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.04 Å | |||||||||
Authors | Ruf, S. / Buning, C. / Schreuder, H. / Horstick, G. / Linz, W. / Olpp, T. / Pernerstorfer, J. / Hiss, K. / Kroll, K. / Kannt, A. ...Ruf, S. / Buning, C. / Schreuder, H. / Horstick, G. / Linz, W. / Olpp, T. / Pernerstorfer, J. / Hiss, K. / Kroll, K. / Kannt, A. / Kohlmann, M. / Linz, D. / Huebschle, T. / Ruetten, H. / Wirth, K. / Schmidt, T. / Sadowski, T. | |||||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Novel Beta-Amino Acid Derivatives as Inhibitors of Cathepsin A. Authors: Ruf, S. / Buning, C. / Schreuder, H. / Horstick, G. / Linz, W. / Olpp, T. / Pernerstorfer, J. / Hiss, K. / Kroll, K. / Kannt, A. / Kohlmann, M. / Linz, D. / Hubschle, T. / Rutten, H. / ...Authors: Ruf, S. / Buning, C. / Schreuder, H. / Horstick, G. / Linz, W. / Olpp, T. / Pernerstorfer, J. / Hiss, K. / Kroll, K. / Kannt, A. / Kohlmann, M. / Linz, D. / Hubschle, T. / Rutten, H. / Wirth, K. / Schmidt, T. / Sadowski, T. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4az3.cif.gz | 114.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4az3.ent.gz | 84.3 KB | Display | PDB format |
PDBx/mmJSON format | 4az3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4az3_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 4az3_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 4az3_validation.xml.gz | 22.2 KB | Display | |
Data in CIF | 4az3_validation.cif.gz | 33.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/az/4az3 ftp://data.pdbj.org/pub/pdb/validation_reports/az/4az3 | HTTPS FTP |
-Related structure data
Related structure data | 4az0C 1ivyS 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 on special symmetry positions |
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-Components
-LYSOSOMAL PROTECTIVE PROTEIN ... , 2 types, 2 molecules AB
#1: Protein | Mass: 33773.734 Da / Num. of mol.: 1 / Fragment: ACTIVATED PROTEASE RESIDUES 29-326 Source method: isolated from a genetically manipulated source Details: ACTIVATED WITH TRYPSIN-SEPHAROSE / Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P10619, carboxypeptidase C |
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#2: Protein | Mass: 18073.738 Da / Num. of mol.: 1 / Fragment: ACTIVATED PROTEASE, RESIDUES 327-480 Source method: isolated from a genetically manipulated source Details: ACTIVATED WITH TRYPSIN-SEPHAROSE / Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P10619, carboxypeptidase C |
-Sugars , 1 types, 2 molecules
#3: Polysaccharide | Source method: isolated from a genetically manipulated source |
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-Non-polymers , 3 types, 427 molecules
#4: Chemical | ChemComp-S35 / ( | ||
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#5: Chemical | ChemComp-CD / #6: Water | ChemComp-HOH / | |
-Details
Sequence details | EXTRA C-TERMINAL GLU AS LEFTOVER FROM MYC-TAG |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.4 Å3/Da / Density % sol: 48.7 % / Description: NONE |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 4.6 Details: CATA WAS CRYSTALLIZED USING THE HANGING DROP METHOD: 1 UL OF PROTEIN SOLUTION, CONTAINING 6.5 MG/ML CATHEPSIN A, 25 MM TRIS-HCL (PH 8.0) AND 300 MM NACL, WAS MIXED WITH 1 UL RESERVOIR ...Details: CATA WAS CRYSTALLIZED USING THE HANGING DROP METHOD: 1 UL OF PROTEIN SOLUTION, CONTAINING 6.5 MG/ML CATHEPSIN A, 25 MM TRIS-HCL (PH 8.0) AND 300 MM NACL, WAS MIXED WITH 1 UL RESERVOIR SOLUTION, CONTAINING 100 MM NAACETATE (PH 4.5), 18-20% PEG400 AND 100 MM CDCL2, AND SET TO EQUILIBRATE AT 4 DEG. C. ROD-SHAPED CRYSTALS APPEARED IN ABOUT ONE WEEK. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.9395 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 17, 2009 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9395 Å / Relative weight: 1 |
Reflection | Resolution: 2.04→67.1 Å / Num. obs: 27381 / % possible obs: 99 % / Observed criterion σ(I): -3 / Redundancy: 3.7 % / Biso Wilson estimate: 27.96 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 14.9 |
Reflection shell | Resolution: 2.04→2.1 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.35 / Mean I/σ(I) obs: 4 / % possible all: 99.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: MODEL DERIVED FROM PDB ENTRY 1IVY Resolution: 2.04→47.36 Å / Cor.coef. Fo:Fc: 0.9447 / Cor.coef. Fo:Fc free: 0.9265 / SU R Cruickshank DPI: 0.218 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.234 / SU Rfree Blow DPI: 0.167 / SU Rfree Cruickshank DPI: 0.164 Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. RESIDUE TYPES WITHOUT CCP4 ATOM TYPE IN LIBRARY=CD. NUMBER OF ATOMS WITH PROPER CCP4 ATOM TYPE=3850. NUMBER WITH APPROX DEFAULT CCP4 ATOM TYPE=0. ...Details: IDEAL-DIST CONTACT TERM CONTACT SETUP. RESIDUE TYPES WITHOUT CCP4 ATOM TYPE IN LIBRARY=CD. NUMBER OF ATOMS WITH PROPER CCP4 ATOM TYPE=3850. NUMBER WITH APPROX DEFAULT CCP4 ATOM TYPE=0. NUMBER TREATED BY BAD NON-BONDED CONTACTS=4.
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Displacement parameters | Biso mean: 28.88 Å2
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Refine analyze | Luzzati coordinate error obs: 0.244 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.04→47.36 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.04→2.12 Å / Total num. of bins used: 14
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