[English] 日本語
Yorodumi
- PDB-7pr8: Crystal structure of human heparanase in complex with covalent in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7pr8
TitleCrystal structure of human heparanase in complex with covalent inhibitor GR109
Components
  • Heparanase 50 kDa subunit
  • Heparanase 8 kDa subunit
KeywordsCARBOHYDRATE / glycoside hydrolase / glucuronidase / GH79 / heparan sulfate
Function / homology
Function and homology information


heparanase / heparanase activity / regulation of hair follicle development / heparin proteoglycan metabolic process / heparan sulfate proteoglycan catabolic process / beta-glucuronidase activity / HS-GAG degradation / positive regulation of hair follicle development / syndecan binding / proteoglycan metabolic process ...heparanase / heparanase activity / regulation of hair follicle development / heparin proteoglycan metabolic process / heparan sulfate proteoglycan catabolic process / beta-glucuronidase activity / HS-GAG degradation / positive regulation of hair follicle development / syndecan binding / proteoglycan metabolic process / vascular wound healing / protein transmembrane transport / establishment of endothelial barrier / angiogenesis involved in wound healing / positive regulation of osteoblast proliferation / positive regulation of vascular endothelial growth factor production / positive regulation of blood coagulation / extracellular matrix / lysosomal lumen / cell-matrix adhesion / specific granule lumen / lysosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / membrane raft / lysosomal membrane / response to antibiotic / intracellular membrane-bounded organelle / Neutrophil degranulation / extracellular space / extracellular region / nucleoplasm / nucleus
Similarity search - Function
Glycoside hydrolase, family 79 / Glycosyl hydrolase family 79, N-terminal domain / Glycosidases / Glycoside hydrolase superfamily / TIM Barrel / Alpha-Beta Barrel / Alpha Beta
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.66 Å
AuthorsWu, L. / Armstrong, Z. / Davies, G.J.
Funding support United Kingdom, 7items
OrganizationGrant numberCountry
European Research Council (ERC)ERC-2011-AdG-290836 United Kingdom
European Research Council (ERC)ERC-2012-AdG-322942 United Kingdom
Netherlands Organisation for Scientific Research (NWO) United Kingdom
Israel Science Foundation1021/19 United Kingdom
European Molecular Biology Organization (EMBO)STF8184 United Kingdom
Royal Society United Kingdom
Wellcome Trust218579/Z/19/Z United Kingdom
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2022
Title: Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo.
Authors: de Boer, C. / Armstrong, Z. / Lit, V.A.J. / Barash, U. / Ruijgrok, G. / Boyango, I. / Weitzenberg, M.M. / Schroder, S.P. / Sarris, A.J.C. / Meeuwenoord, N.J. / Bule, P. / Kayal, Y. / Ilan, N. ...Authors: de Boer, C. / Armstrong, Z. / Lit, V.A.J. / Barash, U. / Ruijgrok, G. / Boyango, I. / Weitzenberg, M.M. / Schroder, S.P. / Sarris, A.J.C. / Meeuwenoord, N.J. / Bule, P. / Kayal, Y. / Ilan, N. / Codee, J.D.C. / Vlodavsky, I. / Overkleeft, H.S. / Davies, G.J. / Wu, L.
History
DepositionSep 21, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 3, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Oct 9, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Heparanase 50 kDa subunit
B: Heparanase 8 kDa subunit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,53914
Polymers51,6082
Non-polymers1,93012
Water5,549308
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, both subunits elute in a single peak at the expected retention time
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10990 Å2
ΔGint-29 kcal/mol
Surface area19180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.490, 71.290, 79.070
Angle α, β, γ (deg.)90.000, 95.200, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein Heparanase 50 kDa subunit


Mass: 43334.898 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9Y251
#2: Protein Heparanase 8 kDa subunit


Mass: 8273.514 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HPSE, HEP, HPA, HPA1, HPR1, HPSE1, HSE1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9Y251

-
Sugars , 3 types, 5 molecules

#3: Polysaccharide alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 367.349 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
LFucpa1-6DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-2/a6-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(6+1)][a-L-Fucp]{}}}LINUCSPDB-CARE
#4: Polysaccharide 2-acetamido-2-deoxy-6-O-sulfo-alpha-D-glucopyranose-(1-4)-(2R,3S,5R,6R)-2,3,4,5,6-pentakis(oxidanyl) ...2-acetamido-2-deoxy-6-O-sulfo-alpha-D-glucopyranose-(1-4)-(2R,3S,5R,6R)-2,3,4,5,6-pentakis(oxidanyl)cyclohexane-1-carboxylic acid


Type: oligosaccharide / Mass: 491.422 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
WURCS=2.0/1,1,0/[a2122h-1a_1-5_1*OC^RC^SC^RC^SC^SC^R$3/8O/7O/6O/5O/4CO/13=O_2*NCC/3=O_6*OSO/3=O/3=O]/1/WURCSPDB2Glycan 1.1.0
[][<C7O5>]{[(1+1)][a-D-GlcpNAc6SO3]{}}LINUCSPDB-CARE
#5: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 3 types, 315 molecules

#6: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6O2
#7: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 308 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.53 Å3/Da / Density % sol: 51.35 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1 M MES pH 5.5, 0.1 M MgCl2, 17% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97933 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 30, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97933 Å / Relative weight: 1
ReflectionResolution: 1.66→39.37 Å / Num. obs: 59928 / % possible obs: 98.6 % / Redundancy: 4.2 % / CC1/2: 0.999 / Rmerge(I) obs: 0.052 / Rpim(I) all: 0.029 / Net I/σ(I): 12.5
Reflection shellResolution: 1.66→1.7 Å / Rmerge(I) obs: 1.415 / Mean I/σ(I) obs: 1 / Num. unique obs: 4353 / CC1/2: 0.532 / Rpim(I) all: 0.789

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
xia2data reduction
Aimlessdata scaling
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5e8m

5e8m


Resolution: 1.66→39.37 Å / Cor.coef. Fo:Fc: 0.976 / Cor.coef. Fo:Fc free: 0.967 / SU B: 2.738 / SU ML: 0.084 / Cross valid method: FREE R-VALUE / ESU R: 0.091 / ESU R Free: 0.089
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.1943 3027 5.052 %
Rwork0.1666 56894 -
all0.168 --
obs-59921 98.579 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 36.497 Å2
Baniso -1Baniso -2Baniso -3
1-2.611 Å2-0 Å21.759 Å2
2---2.022 Å20 Å2
3----0.894 Å2
Refinement stepCycle: LAST / Resolution: 1.66→39.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3643 0 122 308 4073
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0133932
X-RAY DIFFRACTIONr_bond_other_d0.0010.0173749
X-RAY DIFFRACTIONr_angle_refined_deg1.6941.6965342
X-RAY DIFFRACTIONr_angle_other_deg1.3751.6188665
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8095467
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.12121.858183
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.13515654
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.0931522
X-RAY DIFFRACTIONr_chiral_restr0.280.2515
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.024850
X-RAY DIFFRACTIONr_gen_planes_other0.0030.02904
X-RAY DIFFRACTIONr_nbd_refined0.2050.2740
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1780.23475
X-RAY DIFFRACTIONr_nbtor_refined0.1710.21907
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0870.21821
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1590.2242
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.040.24
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1750.219
X-RAY DIFFRACTIONr_nbd_other0.2480.261
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2170.212
X-RAY DIFFRACTIONr_mcbond_it2.9213.4711859
X-RAY DIFFRACTIONr_mcbond_other2.9173.4681858
X-RAY DIFFRACTIONr_mcangle_it3.9325.1892329
X-RAY DIFFRACTIONr_mcangle_other3.9335.1912330
X-RAY DIFFRACTIONr_scbond_it4.0954.0132073
X-RAY DIFFRACTIONr_scbond_other4.0944.0142074
X-RAY DIFFRACTIONr_scangle_it6.0875.8183013
X-RAY DIFFRACTIONr_scangle_other6.0865.823014
X-RAY DIFFRACTIONr_lrange_it7.60642.0124323
X-RAY DIFFRACTIONr_lrange_other7.60642.0214324
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.66-1.7030.3432410.3324104X-RAY DIFFRACTION97.7283
1.703-1.750.3342010.3114065X-RAY DIFFRACTION98.0239
1.75-1.80.2831900.2834004X-RAY DIFFRACTION98.1971
1.8-1.8560.282070.2443836X-RAY DIFFRACTION98.2264
1.856-1.9170.2412110.2083696X-RAY DIFFRACTION98.2893
1.917-1.9840.2342000.23608X-RAY DIFFRACTION98.271
1.984-2.0590.2191610.1713518X-RAY DIFFRACTION98.8182
2.059-2.1430.1971560.1673406X-RAY DIFFRACTION98.7251
2.143-2.2380.2111820.1573207X-RAY DIFFRACTION98.4316
2.238-2.3470.2231560.1583094X-RAY DIFFRACTION98.9044
2.347-2.4740.1791750.1542938X-RAY DIFFRACTION98.6063
2.474-2.6240.1781750.1542766X-RAY DIFFRACTION99.1571
2.624-2.8050.2091540.1632599X-RAY DIFFRACTION98.922
2.805-3.0290.2081230.1642474X-RAY DIFFRACTION99.1979
3.029-3.3180.1861260.1672271X-RAY DIFFRACTION99.2958
3.318-3.7080.2960.1682042X-RAY DIFFRACTION98.8442
3.708-4.2810.1541110.1321812X-RAY DIFFRACTION99.4827
4.281-5.2390.128760.1271556X-RAY DIFFRACTION99.4516
5.239-7.3920.206530.1741207X-RAY DIFFRACTION99.5261
7.392-39.370.162330.154691X-RAY DIFFRACTION98.9071

+
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://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