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- PDB-4o3u: Zymogen HGF-beta/MET with Zymogen Activator Peptide ZAP2.3 -

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Basic information

Entry
Database: PDB / ID: 4o3u
TitleZymogen HGF-beta/MET with Zymogen Activator Peptide ZAP2.3
Components
  • Hepatocyte growth factor receptorC-Met
  • Hepatocyte growth factor
  • ZAP 2.3
Keywordstransferase/growth factor / trypsin homoloy / receptor activation / transferase-growth factor complex
Function / homology
Function and homology information


regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins ...regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / hepatocyte growth factor receptor activity / negative regulation of guanyl-nucleotide exchange factor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / hepatocyte growth factor receptor signaling pathway / semaphorin receptor activity / positive regulation of endothelial cell chemotaxis / MET receptor recycling / pancreas development / MET activates PTPN11 / MET activates RAP1 and RAC1 / Sema4D mediated inhibition of cell attachment and migration / myoblast proliferation / MET activates PI3K/AKT signaling / negative regulation of stress fiber assembly / negative regulation of Rho protein signal transduction / MET activates PTK2 signaling / positive regulation of DNA biosynthetic process / cellular response to hepatocyte growth factor stimulus / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of thrombin-activated receptor signaling pathway / negative regulation of release of cytochrome c from mitochondria / chemoattractant activity / negative regulation of interleukin-6 production / semaphorin-plexin signaling pathway / positive regulation of interleukin-10 production / epithelial to mesenchymal transition / establishment of skin barrier / positive regulation of osteoblast differentiation / MET activates RAS signaling / negative regulation of peptidyl-serine phosphorylation / phagocytosis / MECP2 regulates neuronal receptors and channels / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of microtubule polymerization / Interleukin-7 signaling / cell chemotaxis / basal plasma membrane / negative regulation of autophagy / InlB-mediated entry of Listeria monocytogenes into host cell / platelet alpha granule lumen / liver development / epithelial cell proliferation / molecular function activator activity / growth factor activity / cell morphogenesis / Negative regulation of MET activity / receptor protein-tyrosine kinase / neuron differentiation / negative regulation of inflammatory response / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / positive regulation of peptidyl-tyrosine phosphorylation / cell migration / Platelet degranulation / PIP3 activates AKT signaling / mitotic cell cycle / nervous system development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / positive regulation of MAPK cascade / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of cell migration / positive regulation of protein phosphorylation / phosphorylation / signaling receptor binding / negative regulation of apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / ATP binding / membrane / identical protein binding / plasma membrane
Similarity search - Function
Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / divergent subfamily of APPLE domains / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain ...Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / ligand-binding face of the semaphorins, domain 2 / ligand-binding face of the semaphorins, domain 2 / divergent subfamily of APPLE domains / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / IPT/TIG domain / ig-like, plexins, transcription factors / PSI domain / domain found in Plexins, Semaphorins and Integrins / IPT domain / YVTN repeat-like/Quinoprotein amine dehydrogenase / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / 7 Propeller / Methylamine Dehydrogenase; Chain H / Kringle-like fold / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Immunoglobulin E-set / Trypsin / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Trypsin-like serine proteases / Tyrosine-protein kinase, active site / Thrombin, subunit H / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / WD40/YVTN repeat-like-containing domain superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Peptidase S1, PA clan / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Beta Barrel / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Hepatocyte growth factor receptor / Hepatocyte growth factor
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.04 Å
AuthorsEigenbrot, C. / Landgraf, K.E. / Steffek, M.
CitationJournal: Nat.Chem.Biol. / Year: 2014
Title: An allosteric switch for pro-HGF/Met signaling using zymogen activator peptides.
Authors: Landgraf, K.E. / Steffek, M. / Quan, C. / Tom, J. / Yu, C. / Santell, L. / Maun, H.R. / Eigenbrot, C. / Lazarus, R.A.
History
DepositionDec 18, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 4, 2014Provider: repository / Type: Initial release
Revision 1.1Jul 2, 2014Group: Database references
Revision 1.2Sep 20, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Hepatocyte growth factor
B: Hepatocyte growth factor receptor
P: ZAP 2.3


Theoretical massNumber of molelcules
Total (without water)91,3013
Polymers91,3013
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)136.105, 139.620, 66.144
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

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Components

#1: Protein Hepatocyte growth factor / / Hepatopoietin-A / Scatter factor / SF / Hepatocyte growth factor alpha chain / Hepatocyte growth ...Hepatopoietin-A / Scatter factor / SF / Hepatocyte growth factor alpha chain / Hepatocyte growth factor beta chain


Mass: 26800.920 Da / Num. of mol.: 1 / Fragment: HGF-beta (UNP Residues 25-567) / Mutation: V495G/C604S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HGF, HPTA / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P14210
#2: Protein Hepatocyte growth factor receptor / C-Met / HGF receptor / HGF/SF receptor / Proto-oncogene c-Met / Scatter factor receptor / SF receptor / ...HGF receptor / HGF/SF receptor / Proto-oncogene c-Met / Scatter factor receptor / SF receptor / Tyrosine-protein kinase Met


Mass: 62714.141 Da / Num. of mol.: 1 / Fragment: Sema-PSI (UNP Residues 496-728) / Mutation: L303K/V304R/P305K/R306K/G307R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MET / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P08581, receptor protein-tyrosine kinase
#3: Protein/peptide ZAP 2.3


Mass: 1786.081 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: synthetic peptide library displayed on phage / Source: (synth.) synthetic (others)

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 3.44 Å3/Da / Density % sol: 64.26 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.2
Details: 8% PEG8000, pH 7.2, VAPOR DIFFUSION, SITTING DROP, temperature 293K

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Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.9794 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: May 23, 2012
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9794 Å / Relative weight: 1
ReflectionResolution: 3.04→34.76 Å / Num. all: 24419 / Num. obs: 24340 / % possible obs: 97.5 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.6 % / Biso Wilson estimate: 102.77 Å2 / Rsym value: 0.056 / Net I/σ(I): 23

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Processing

Software
NameVersionClassification
Blu-Icedata collection
PHASERphasing
BUSTER2.11.2refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1SHY
Resolution: 3.04→34.76 Å / Cor.coef. Fo:Fc: 0.8969 / Cor.coef. Fo:Fc free: 0.8574 / SU R Cruickshank DPI: 1.39 / Isotropic thermal model: individual atom isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2507 1007 4.14 %RANDOM
Rwork0.2069 ---
all0.223 24419 --
obs0.2087 24340 97.52 %-
Displacement parametersBiso mean: 94.12 Å2
Baniso -1Baniso -2Baniso -3
1--10.9442 Å20 Å20 Å2
2--35.5448 Å20 Å2
3----24.6007 Å2
Refine analyzeLuzzati coordinate error obs: 0.593 Å
Refinement stepCycle: LAST / Resolution: 3.04→34.76 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5786 0 0 0 5786
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0095945HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.248073HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2012SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes142HARMONIC2
X-RAY DIFFRACTIONt_gen_planes862HARMONIC5
X-RAY DIFFRACTIONt_it5945HARMONIC20
X-RAY DIFFRACTIONt_omega_torsion2.8
X-RAY DIFFRACTIONt_other_torsion23.43
X-RAY DIFFRACTIONt_chiral_improper_torsion766SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact6369SEMIHARMONIC4
LS refinement shellResolution: 3.04→3.17 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.3238 93 3.22 %
Rwork0.2424 2794 -
all0.2449 2887 -
obs-2887 97.52 %

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