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Open data
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Basic information
Entry | Database: PDB / ID: 2c0i | ||||||
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Title | Src family kinase Hck with bound inhibitor A-420983 | ||||||
![]() | TYROSINE-PROTEIN KINASE HCK | ||||||
![]() | TRANSFERASE / TYROSINE-PROTEIN KINASE / ATP-BINDING / KINASE / LIPOPROTEIN / MYRISTATE / NUCLEOTIDE-BINDING / PALMITATE / PHOSPHORYLATION / SH2 DOMAIN / SH3 DOMAIN | ||||||
Function / homology | ![]() leukocyte degranulation / respiratory burst after phagocytosis / innate immune response-activating signaling pathway / leukocyte migration involved in immune response / regulation of podosome assembly / regulation of phagocytosis / FLT3 signaling through SRC family kinases / Nef and signal transduction / regulation of DNA-binding transcription factor activity / positive regulation of actin filament polymerization ...leukocyte degranulation / respiratory burst after phagocytosis / innate immune response-activating signaling pathway / leukocyte migration involved in immune response / regulation of podosome assembly / regulation of phagocytosis / FLT3 signaling through SRC family kinases / Nef and signal transduction / regulation of DNA-binding transcription factor activity / positive regulation of actin filament polymerization / Fc-gamma receptor signaling pathway involved in phagocytosis / mesoderm development / FCGR activation / localization / type II interferon-mediated signaling pathway / Signaling by CSF3 (G-CSF) / lipopolysaccharide-mediated signaling pathway / transport vesicle / extrinsic component of cytoplasmic side of plasma membrane / negative regulation of inflammatory response to antigenic stimulus / cell surface receptor protein tyrosine kinase signaling pathway / phosphotyrosine residue binding / FCGR3A-mediated IL10 synthesis / caveola / cell projection / integrin-mediated signaling pathway / Regulation of signaling by CBL / regulation of actin cytoskeleton organization / FCGR3A-mediated phagocytosis / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / cytoplasmic side of plasma membrane / cytokine-mediated signaling pathway / peptidyl-tyrosine phosphorylation / Signaling by CSF1 (M-CSF) in myeloid cells / regulation of cell shape / regulation of inflammatory response / protein tyrosine kinase activity / protein autophosphorylation / lysosome / cell differentiation / cytoskeleton / cell adhesion / intracellular signal transduction / inflammatory response / protein phosphorylation / intracellular membrane-bounded organelle / innate immune response / focal adhesion / signaling receptor binding / lipid binding / positive regulation of cell population proliferation / negative regulation of apoptotic process / Golgi apparatus / ATP binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Borhani, D.W. / Burchat, A. / Calderwood, D.J. / Hirst, G.C. / Li, B. / Loew, A. | ||||||
![]() | ![]() Title: Discovery of A-770041, a Src-Family Selective Orally Active Lck Inhibitor that Prevents Organ Allograft Rejection. Authors: Burchat, A. / Borhani, D.W. / Calderwood, D.J. / Hirst, G.C. / Li, B. / Stachlewitz, R.F. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2004 Title: A-420983: A Potent, Orally Active Inhibitor of Lck with Efficacy in a Model of Transplant Rejection Authors: Borhani, D.W. / Calderwood, D.J. / Friedman, M.M. / Hirst, G.C. / Li, B. / Leung, A.K.W. / Mcrae, B. / Ratnofsky, S. / Ritter, K. / Waegell, W. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 196.7 KB | Display | ![]() |
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PDB format | ![]() | 155.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 874.8 KB | Display | ![]() |
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Full document | ![]() | 892.8 KB | Display | |
Data in XML | ![]() | 36.2 KB | Display | |
Data in CIF | ![]() | 51.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 2c0oC ![]() 2c0tC ![]() 1ad5S S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1
NCS ensembles :
NCS oper: (Code: given Matrix: (0.944154, 0.025026, -0.328552), Vector: |
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Components
#1: Protein | Mass: 52000.227 Da / Num. of mol.: 2 / Fragment: SH3-SH2-SH1, RESIDUES 80-525 / Mutation: YES Source method: isolated from a genetically manipulated source Details: SRC NUMBERING USED. ADD 20 TO THE RESIDUE NUMBERS IN THIS ENTRY TO OBTAIN ACTUAL HUMAN HCK RESIDUE NUMBERS. RESIDUE Y501 (HCK Y521) IS PHOSPHORYLATED Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Compound details | ENGINEERED RESIDUE IN CHAIN A, GLN 502 TO GLU ENGINEERED RESIDUE IN CHAIN A, GLN 503 TO GLU ...ENGINEERED | Sequence details | THE PROTEIN CRYSTALLIZED INCLUDED EIGHT NON-NATIVE N-TERMINAL RESIDUES: GLY-ALA-MET-GLY-SER-GLY-ILE- ...THE PROTEIN CRYSTALLIZ | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.1 Å3/Da / Density % sol: 59.9 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 Details: HCK (10 MG/ML IN 150 MM NACL, 20 MM TRIS.HCL PH 8.0) WAS MIXED WITH A-420983 [100 MM STOCK SOLUTION OF THE BIS-MALEIC ACID SALT IN DMSO) TO GIVE A FINAL A-420983 CONCENTRATION OF 1 MM. HCK/A- ...Details: HCK (10 MG/ML IN 150 MM NACL, 20 MM TRIS.HCL PH 8.0) WAS MIXED WITH A-420983 [100 MM STOCK SOLUTION OF THE BIS-MALEIC ACID SALT IN DMSO) TO GIVE A FINAL A-420983 CONCENTRATION OF 1 MM. HCK/A-420983 WAS THEN MIXED WITH RESERVOIR SOLUTION (12% PEG 6000, 3% 1, 5-DIAMINOPENTANE, 20% GLYCEROL, 200 MM CA(OAC)2, 100 MM TRIS.HCL PH 8.0) AND EQUILBRATED AGAINST THE RESERVOIR SOLUTION BY VAPOR DIFFUSION (SITTING DROPS) AT 277 K. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: MARRESEARCH / Detector: CCD / Date: Feb 7, 2002 |
Radiation | Monochromator: SI(111) DOUBLE MONOCHROMATOR / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→15 Å / Num. obs: 50423 / % possible obs: 88.9 % / Observed criterion σ(I): 0 / Redundancy: 2.5 % / Biso Wilson estimate: 54.7 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 13.8 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 2.1 % / Rmerge(I) obs: 0.28 / Mean I/σ(I) obs: 3.3 / % possible all: 75.5 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB ENTRY 1AD5 Resolution: 2.3→19.96 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.91 / SU B: 15.259 / SU ML: 0.192 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.341 / ESU R Free: 0.261 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. THE ACTIVATION LOOP (RESIDUES A386-A398 AND B386-B398) IS DISORDERED IN BOTH HCK MOLECULES (CHAINS A AND B). HCK CHAIN A IS SLIGHTLY BETTER ...Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. THE ACTIVATION LOOP (RESIDUES A386-A398 AND B386-B398) IS DISORDERED IN BOTH HCK MOLECULES (CHAINS A AND B). HCK CHAIN A IS SLIGHTLY BETTER ORDERED THAN CHAIN B. SIMILARLY, THE LIGAND A1506 IS BETTER ORDERED THAN B1506. SEVEN N-TERMINAL RESIDUES (FROM THE EXPRESSION VECTOR, GLY-ALA -MET-GLY-SER-GLY-ILE) ARE DISORDERED IN BOTH CHAINS. RESIDUE ARG-59 IS NON-NATIVE (EXPRESSION VECTOR).
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 50.47 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→19.96 Å
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Refine LS restraints |
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