[English] 日本語
Yorodumi
- PDB-6ql8: Cathepsin-K in complex with MIV-711 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ql8
TitleCathepsin-K in complex with MIV-711
ComponentsCathepsin K
KeywordsHYDROLASE / inhibitor complex / lysosomal cysteine proteinase
Function / homology
Function and homology information


cathepsin K / mononuclear cell differentiation / intramembranous ossification / negative regulation of cartilage development / cellular response to zinc ion starvation / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / thyroid hormone generation / endolysosome lumen / Trafficking and processing of endosomal TLR / proteoglycan binding ...cathepsin K / mononuclear cell differentiation / intramembranous ossification / negative regulation of cartilage development / cellular response to zinc ion starvation / RUNX1 regulates transcription of genes involved in differentiation of keratinocytes / thyroid hormone generation / endolysosome lumen / Trafficking and processing of endosomal TLR / proteoglycan binding / Activation of Matrix Metalloproteinases / cysteine-type endopeptidase activator activity involved in apoptotic process / mitophagy / fibronectin binding / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / cysteine-type peptidase activity / bone resorption / cellular response to transforming growth factor beta stimulus / collagen binding / MHC class II antigen presentation / Degradation of the extracellular matrix / lysosomal lumen / proteolysis involved in protein catabolic process / positive regulation of apoptotic signaling pathway / response to insulin / response to organic cyclic compound / cellular response to tumor necrosis factor / response to ethanol / lysosome / immune response / apical plasma membrane / external side of plasma membrane / cysteine-type endopeptidase activity / intracellular membrane-bounded organelle / serine-type endopeptidase activity / proteolysis / extracellular space / extracellular region / nucleoplasm
Similarity search - Function
Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Papain-like cysteine endopeptidase / : / Cysteine peptidase, asparagine active site / Eukaryotic thiol (cysteine) proteases asparagine active site. / Cysteine peptidase, histidine active site / Eukaryotic thiol (cysteine) proteases histidine active site. / Peptidase C1A, papain C-terminal ...Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Cathepsin propeptide inhibitor domain (I29) / Papain-like cysteine endopeptidase / : / Cysteine peptidase, asparagine active site / Eukaryotic thiol (cysteine) proteases asparagine active site. / Cysteine peptidase, histidine active site / Eukaryotic thiol (cysteine) proteases histidine active site. / Peptidase C1A, papain C-terminal / Papain family cysteine protease / Papain family cysteine protease / Cysteine proteinases / Cysteine peptidase, cysteine active site / Eukaryotic thiol (cysteine) proteases cysteine active site. / Cathepsin B; Chain A / Papain-like cysteine peptidase superfamily / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
Chem-J5N / NITRATE ION / Cathepsin K
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.8 Å
AuthorsDerbyshire, D.J.
CitationJournal: To Be Published
Title: Successful development of 3-oxohexahydrofuropyrrole amino acid amides as inhibitors of Cathepsin-K.
Authors: Derbyshire, D.J.
History
DepositionJan 31, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 19, 2020Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Cathepsin K
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,6798
Polymers23,7381
Non-polymers9427
Water4,684260
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1140 Å2
ΔGint10 kcal/mol
Surface area10150 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.910, 70.910, 54.270
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number78
Space group name H-MP43

-
Components

#1: Protein Cathepsin K / Cathepsin O / Cathepsin O2 / Cathepsin X


Mass: 23737.727 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CTSK, CTSO, CTSO2 / Plasmid: pET16b / Production host: Escherichia coli (E. coli) / References: UniProt: P43235, cathepsin K
#2: Chemical ChemComp-J5N / ~{N}-[(2~{S})-1-[(3~{R},3~{a}~{R},6~{R},6~{a}~{R})-6-ethynyl-3-oxidanyl-2,3,3~{a},5,6,6~{a}-hexahydrofuro[3,2-b]pyrrol-4-yl]-4-methyl-1-oxidanylidene-pentan-2-yl]-4-[5-fluoranyl-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide


Mass: 569.691 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H36FN5O4S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-NO3 / NITRATE ION


Mass: 62.005 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: NO3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 260 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.87 Å3/Da / Density % sol: 57.2 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 100mM ADA pH6.0, 500mM ammonium nitrate, 17% PEG 3350
PH range: 6.0-6.2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.0723 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Feb 11, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0723 Å / Relative weight: 1
ReflectionResolution: 1.8→70.91 Å / Num. obs: 24605 / % possible obs: 98.1 % / Redundancy: 3.9 % / CC1/2: 0.992 / Rmerge(I) obs: 0.117 / Rpim(I) all: 0.067 / Rrim(I) all: 0.136 / Net I/σ(I): 8.5 / Num. measured all: 96143 / Scaling rejects: 8
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all% possible all
1.8-1.843.30.70311800.5550.4240.82481.7
9-70.913.70.0342170.9980.0190.03998.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
MOSFLMdata reduction
Aimless0.5.32data scaling
PHASERphasing
REFMAC5.8.0158refinement
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.8→70.91 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.947 / SU B: 4.158 / SU ML: 0.066 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.099 / ESU R Free: 0.098
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.1811 1263 5.1 %RANDOM
Rwork0.149 ---
obs0.1506 23335 97.98 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.3 Å
Displacement parametersBiso max: 65.3 Å2 / Biso mean: 17.394 Å2 / Biso min: 8.23 Å2
Baniso -1Baniso -2Baniso -3
1-0.01 Å2-0 Å2-0 Å2
2--0.01 Å2-0 Å2
3----0.02 Å2
Refinement stepCycle: final / Resolution: 1.8→70.91 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1664 0 64 260 1988
Biso mean--19.79 28.36 -
Num. residues----217
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.021786
X-RAY DIFFRACTIONr_bond_other_d0.0020.021583
X-RAY DIFFRACTIONr_angle_refined_deg1.3671.9812410
X-RAY DIFFRACTIONr_angle_other_deg0.8983.0013700
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4435221
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.3312580
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.20715296
X-RAY DIFFRACTIONr_dihedral_angle_4_deg7.143158
X-RAY DIFFRACTIONr_chiral_restr0.0770.2241
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022022
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02354
LS refinement shellResolution: 1.8→1.847 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.34 74 -
Rwork0.286 1442 -
all-1516 -
obs--82.12 %
Refinement TLS params.Method: refined / Origin x: 27.944 Å / Origin y: 13.763 Å / Origin z: 26.661 Å
111213212223313233
T0.023 Å2-0.002 Å20.0049 Å2-0.0105 Å2-0.0092 Å2--0.0208 Å2
L0.8095 °2-0.4493 °20.1926 °2-1.1966 °2-0.4278 °2--1.0878 °2
S-0.0146 Å °0.006 Å °0.018 Å °0.0656 Å °0.0049 Å °0.0613 Å °-0.0408 Å °-0.061 Å °0.0097 Å °

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more