[English] 日本語
Yorodumi
- PDB-8g24: Crystal Structure of Cathepsin-G and Neutrophil Elastase Inhibite... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8g24
TitleCrystal Structure of Cathepsin-G and Neutrophil Elastase Inhibited by S. aureus EapH2 at pH 5.5
Components
  • Cathepsin-G
  • MAP domain-containing protein
  • Neutrophil elastase
KeywordsHYDROLASE/INHIBITOR / Protease Inhibitor / Immune Evasion / Neutrophil / S. aureus / HYDROLASE-INHIBITOR complex
Function / homology
Function and homology information


cathepsin G / biofilm matrix disassembly / neutrophil-mediated killing of gram-positive bacterium / leukocyte elastase / biosynthetic process of antibacterial peptides active against Gram-negative bacteria / neutrophil-mediated killing of fungus / purinergic nucleotide receptor signaling pathway / negative regulation of chemotaxis / acute inflammatory response to antigenic stimulus / negative regulation of T cell activation ...cathepsin G / biofilm matrix disassembly / neutrophil-mediated killing of gram-positive bacterium / leukocyte elastase / biosynthetic process of antibacterial peptides active against Gram-negative bacteria / neutrophil-mediated killing of fungus / purinergic nucleotide receptor signaling pathway / negative regulation of chemotaxis / acute inflammatory response to antigenic stimulus / negative regulation of T cell activation / positive regulation of leukocyte tethering or rolling / response to yeast / leukocyte migration involved in inflammatory response / negative regulation of interleukin-8 production / caspase binding / negative regulation of chemokine production / Suppression of apoptosis / protein metabolic process / neutrophil activation / positive regulation of platelet aggregation / Interleukin-1 processing / Antimicrobial peptides / cytokine binding / pyroptotic inflammatory response / Activation of Matrix Metalloproteinases / neutrophil-mediated killing of gram-negative bacterium / monocyte chemotaxis / Collagen degradation / extracellular matrix disassembly / angiotensin maturation / defense response to fungus / Pyroptosis / Metabolism of Angiotensinogen to Angiotensins / Purinergic signaling in leishmaniasis infection / phagocytosis / response to UV / transcription repressor complex / phagocytic vesicle / Degradation of the extracellular matrix / serine-type peptidase activity / secretory granule / Regulation of Complement cascade / positive regulation of interleukin-8 production / positive regulation of smooth muscle cell proliferation / positive regulation of MAP kinase activity / protein catabolic process / protein processing / platelet activation / cytokine-mediated signaling pathway / negative regulation of inflammatory response / cytoplasmic stress granule / intracellular calcium ion homeostasis / specific granule lumen / transcription corepressor activity / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of immune response / azurophil granule lumen / peptidase activity / heparin binding / antibacterial humoral response / cellular response to lipopolysaccharide / collagen-containing extracellular matrix / defense response to Gram-negative bacterium / endopeptidase activity / protease binding / response to lipopolysaccharide / receptor ligand activity / lysosome / defense response to Gram-positive bacterium / defense response to bacterium / immune response / protein phosphorylation / intracellular membrane-bounded organelle / serine-type endopeptidase activity / Neutrophil degranulation / cell surface / negative regulation of transcription by RNA polymerase II / proteolysis / extracellular space / extracellular exosome / extracellular region / membrane / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
MAP domain / MAP domain / MAP repeat profile. / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease ...MAP domain / MAP domain / MAP repeat profile. / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan
Similarity search - Domain/homology
MAP domain-containing protein / Neutrophil elastase / Cathepsin G
Similarity search - Component
Biological speciesStaphylococcus aureus subsp. aureus Mu50 (bacteria)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.82 Å
AuthorsMishra, N.B. / Geisbrecht, B.V.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM140852 United States
CitationJournal: J.Biol.Chem. / Year: 2023
Title: Simultaneous inhibition of two neutrophil serine proteases by the S. aureus innate immune evasion protein EapH2.
Authors: Mishra, N. / Herdendorf, T.J. / Prakash, O. / Geisbrecht, B.V.
History
DepositionFeb 3, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 26, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jul 19, 2023Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.3Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: MAP domain-containing protein
B: Neutrophil elastase
A: Cathepsin-G
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,2644
Polymers61,8403
Non-polymers4241
Water2,936163
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: assay for oligomerization, funtional assay for enzyme inhibition
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4240 Å2
ΔGint-9 kcal/mol
Surface area23560 Å2
MethodPISA
Unit cell
Length a, b, c (Å)49.070, 68.604, 82.417
Angle α, β, γ (deg.)90.00, 102.52, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein MAP domain-containing protein


Mass: 13123.912 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Staphylococcus aureus subsp. aureus Mu50 (bacteria)
Gene: SAV0981 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: A0A0H3JUK5
#2: Protein Neutrophil elastase / Bone marrow serine protease / Elastase-2 / Human leukocyte elastase / HLE / Medullasin / PMN elastase


Mass: 23318.982 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: neutrophil / References: UniProt: P08246, leukocyte elastase
#3: Protein Cathepsin-G


Mass: 25397.131 Da / Num. of mol.: 1 / Fragment: C-terminal truncation (UNP residues 21-243) / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: neutrophil / References: UniProt: P08311
#4: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 163 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.19 Å3/Da / Density % sol: 43.83 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.1 M Bis-Tris, 0.2 M sodium chloride, 26% w/v PDB3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 9, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.82→50 Å / Num. obs: 47888 / % possible obs: 97.8 % / Redundancy: 3.3 % / CC1/2: 0.985 / Rpim(I) all: 0.057 / Χ2: 0.082 / Net I/σ(I): 10.1 / Num. measured all: 303430
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Num. unique obsCC1/2Rpim(I) allΧ2% possible all
1.82-1.892.991110.4660.5770.97398.1
1.89-1.963.292770.6740.3931.14397.7
1.96-2.053.188900.8240.2621.11395.5
2.05-2.163.693230.9150.1731.03899.9
2.16-2.293.693080.9430.1620.92699.6
2.29-2.473.593140.9620.0981.02299.5
2.47-2.723.492940.9730.0781.09598.8
2.72-3.113.389990.9810.0611.07596.4
3.11-3.923.492380.9880.0471.09698.6
3.92-503.287860.9780.0411.13893.7

-
Processing

Software
NameVersionClassification
PHENIXv1.19.2refinement
SCALEPACKdata scaling
DENZOdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 1AU8, 1HNE, & 1YN5

1au8

1hne

1yn5


Resolution: 1.82→47.9 Å / SU ML: 0.24 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 27.1 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2491 1895 4.23 %
Rwork0.212 --
obs0.2136 44822 93.61 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.82→47.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4235 0 28 163 4426
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0074339
X-RAY DIFFRACTIONf_angle_d0.9535870
X-RAY DIFFRACTIONf_dihedral_angle_d15.9351630
X-RAY DIFFRACTIONf_chiral_restr0.06658
X-RAY DIFFRACTIONf_plane_restr0.009772
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.82-1.870.35931140.34722506X-RAY DIFFRACTION77
1.87-1.920.3111110.30562785X-RAY DIFFRACTION85
1.92-1.970.32041300.2782835X-RAY DIFFRACTION88
1.97-2.040.26671150.27152850X-RAY DIFFRACTION87
2.04-2.110.32091290.24353113X-RAY DIFFRACTION95
2.11-2.190.27341520.23953115X-RAY DIFFRACTION97
2.19-2.290.26681280.2313228X-RAY DIFFRACTION98
2.29-2.420.24861480.21073209X-RAY DIFFRACTION98
2.42-2.570.23951490.22453217X-RAY DIFFRACTION99
2.57-2.760.27271430.22433216X-RAY DIFFRACTION98
2.76-3.040.30451410.23143147X-RAY DIFFRACTION97
3.04-3.480.26891450.21073295X-RAY DIFFRACTION100
3.48-4.390.20511460.17483212X-RAY DIFFRACTION97
4.39-47.90.21961440.19353199X-RAY DIFFRACTION95

+
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