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Yorodumi- PDB-5nx1: Combinatorial Engineering of Proteolytically Resistant APPI Varia... -
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-Basic information
Entry | Database: PDB / ID: 5nx1 | ||||||
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Title | Combinatorial Engineering of Proteolytically Resistant APPI Variants that Selectively Inhibit Human Kallikrein 6 for Cancer Therapy | ||||||
Components |
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Keywords | HYDROLASE / Serine_protease / inhibitor / complex | ||||||
Function / homology | Function and homology information tissue regeneration / positive regulation of G protein-coupled receptor signaling pathway / cornified envelope / regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / collateral sprouting in absence of injury / cytosolic mRNA polyadenylation / microglia development / hormone metabolic process / regulation of synapse structure or activity ...tissue regeneration / positive regulation of G protein-coupled receptor signaling pathway / cornified envelope / regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / collateral sprouting in absence of injury / cytosolic mRNA polyadenylation / microglia development / hormone metabolic process / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / amyloid precursor protein metabolic process / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / regulation of Wnt signaling pathway / mating behavior / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / : / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / intercellular bridge / presynaptic active zone / nuclear envelope lumen / modulation of excitatory postsynaptic potential / suckling behavior / COPII-coated ER to Golgi transport vesicle / regulation of neuron projection development / dendrite development / regulation of cell differentiation / smooth endoplasmic reticulum / regulation of NMDA receptor activity / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / regulation of presynapse assembly / The NLRP3 inflammasome / protein autoprocessing / intracellular copper ion homeostasis / transition metal ion binding / regulation of multicellular organism growth / negative regulation of long-term synaptic potentiation / Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases / negative regulation of neuron differentiation / collagen catabolic process / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / forebrain development / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / positive regulation of G2/M transition of mitotic cell cycle / myelination / ionotropic glutamate receptor signaling pathway / positive regulation of protein metabolic process / neuron projection maintenance / cholesterol metabolic process / extracellular matrix organization / positive regulation of glycolytic process / positive regulation of mitotic cell cycle / response to interleukin-1 / axonogenesis / adult locomotory behavior / trans-Golgi network membrane / dendritic shaft / locomotory behavior / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / secretory granule / learning / central nervous system development / positive regulation of interleukin-1 beta production / positive regulation of long-term synaptic potentiation / astrocyte activation / endosome lumen / synapse organization / Post-translational protein phosphorylation / regulation of long-term neuronal synaptic plasticity / positive regulation of JNK cascade / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / serine-type endopeptidase inhibitor activity / recycling endosome / cognition / response to wounding / positive regulation of inflammatory response Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.853 Å | ||||||
Authors | Shahar, A. / Sananes, A. / Radisky, E.S. / Papo, N. | ||||||
Citation | Journal: J.Biol.Chem. / Year: 2018 Title: A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering. Authors: Sananes, A. / Cohen, I. / Shahar, A. / Hockla, A. / De Vita, E. / Miller, A.K. / Radisky, E.S. / Papo, N. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5nx1.cif.gz | 152.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5nx1.ent.gz | 119.1 KB | Display | PDB format |
PDBx/mmJSON format | 5nx1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nx/5nx1 ftp://data.pdbj.org/pub/pdb/validation_reports/nx/5nx1 | HTTPS FTP |
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-Related structure data
Related structure data | 5nx3C 1aapS 1lo6S 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
#1: Protein | Mass: 24417.695 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KLK6, PRSS18, PRSS9 / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q92876, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases |
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#2: Protein/peptide | Mass: 2945.086 Da / Num. of mol.: 1 / Fragment: UNP residues 289-301 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APP, A4, AD1 / Production host: Komagataella phaffii GS115 (fungus) / References: UniProt: P05067 |
#3: Protein | Mass: 6295.999 Da / Num. of mol.: 1 / Fragment: UNP residues 302-346 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APP, A4, AD1 / Production host: Komagataella phaffii GS115 (fungus) / References: UniProt: P05067 |
#4: Protein | Mass: 9223.071 Da / Num. of mol.: 1 / Fragment: UNP residues 289-346 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APP, A4, AD1 / Production host: Komagataella phaffii GS115 (fungus) / References: UniProt: P05067 |
#5: 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: 2.49 Å3/Da / Density % sol: 50.57 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion Details: 0.2M Ammonium Sulfate, 0.1M Bis-Tris pH 5.5, 25% Polyethylene Glycol 3350 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.969 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 22, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.969 Å / Relative weight: 1 |
Reflection | Resolution: 1.853→47.262 Å / Num. obs: 36867 / % possible obs: 99.52 % / Redundancy: 2 % / Rpim(I) all: 0.031 / Net I/σ(I): 13.48 |
Reflection shell | Resolution: 1.853→1.92 Å / Redundancy: 2 % / Mean I/σ(I) obs: 1.08 / Num. unique all: 3528 / CC1/2: 0.574 / Rpim(I) all: 0.642 / % possible all: 96.37 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1AAP & 1LO6 Resolution: 1.853→47.262 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.78
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.853→47.262 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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