[English] 日本語
Yorodumi
- PDB-1bb0: THROMBIN INHIBITORS WITH RIGID TRIPEPTIDYL ALDEHYDES -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1bb0
TitleTHROMBIN INHIBITORS WITH RIGID TRIPEPTIDYL ALDEHYDES
Components
  • (THROMBIN) x 2
  • HIRUGEN
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of serine-type peptidase activity / cytolysis by host of symbiont cells / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin-activated receptor signaling pathway / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / Defective F8 cleavage by thrombin ...negative regulation of serine-type peptidase activity / cytolysis by host of symbiont cells / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin-activated receptor signaling pathway / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / Defective F8 cleavage by thrombin / ligand-gated ion channel signaling pathway / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / positive regulation of collagen biosynthetic process / negative regulation of platelet activation / negative regulation of blood coagulation / positive regulation of blood coagulation / negative regulation of fibrinolysis / regulation of cytosolic calcium ion concentration / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / fibrinolysis / negative regulation of proteolysis / Intrinsic Pathway of Fibrin Clot Formation / negative regulation of cytokine production involved in inflammatory response / positive regulation of release of sequestered calcium ion into cytosol / Peptide ligand-binding receptors / Regulation of Complement cascade / acute-phase response / positive regulation of receptor signaling pathway via JAK-STAT / Cell surface interactions at the vascular wall / lipopolysaccharide binding / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / platelet activation / positive regulation of protein localization to nucleus / response to wounding / Golgi lumen / antimicrobial humoral immune response mediated by antimicrobial peptide / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of reactive oxygen species metabolic process / blood coagulation / heparin binding / regulation of cell shape / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of protein phosphorylation / toxin activity / positive regulation of cell growth / : / G alpha (q) signalling events / blood microparticle / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / receptor ligand activity / endoplasmic reticulum lumen / signaling receptor binding / serine-type endopeptidase activity / positive regulation of cell population proliferation / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Hirudin / Proteinase inhibitor I14, hirudin / Thrombin inhibitor hirudin / Hirudin/antistatin / Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain ...Hirudin / Proteinase inhibitor I14, hirudin / Thrombin inhibitor hirudin / Hirudin/antistatin / Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Vitamin K-dependent carboxylation domain. / Gla domain profile. / Domain containing Gla (gamma-carboxyglutamate) residues. / Kringle-like fold / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, serine active site. / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Trypsin-like serine proteases / Thrombin, subunit H / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
N-(benzylsulfonyl)-L-norvalyl-N-{(1R)-2-[(3R)-1-carbamimidoylpiperidin-3-yl]-1-formylethyl}glycinamide / Chem-0IV / Prothrombin / Hirudin variant-1
Similarity search - Component
Biological speciesHirudo medicinalis (medicinal leech)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsKrishnan, R. / Zhang, E. / Hakansson, K. / Arni, R.K. / Tulinsky, A. / Lim-Wilby, M.S.L. / Levy, O.E. / Semple, J.E. / Brunck, T.K.
CitationJournal: Biochemistry / Year: 1998
Title: Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes.
Authors: Krishnan, R. / Zhang, E. / Hakansson, K. / Arni, R.K. / Tulinsky, A. / Lim-Wilby, M.S. / Levy, O.E. / Semple, J.E. / Brunck, T.K.
History
DepositionApr 28, 1998Processing site: BNL
Revision 1.0Apr 27, 1999Provider: repository / Type: Initial release
Revision 1.1Mar 24, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 1.3Jul 27, 2011Group: Database references
Revision 1.4Dec 12, 2012Group: Other
Revision 1.5Aug 2, 2023Group: Database references / Derived calculations ...Database references / Derived calculations / Other / Refinement description
Category: database_2 / pdbx_database_status ...database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_conn_type / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.process_site / _pdbx_struct_conn_angle.ptnr1_PDB_ins_code / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_PDB_ins_code / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_ptnr1_PDB_ins_code / _struct_conn.pdbx_ptnr2_PDB_ins_code / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry / _struct_conn_type.id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.6Nov 20, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_entry_details / pdbx_modification_feature
Item: _pdbx_entry_details.has_protein_modification
Remark 650 HELIX DETERMINATION METHOD: TAKEN FROM RELEASED PDB ENTRY 1AY6
Remark 700 SHEET DETERMINATION METHOD: TAKEN FROM RELEASED PDB ENTRY 1AY6

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: THROMBIN
B: THROMBIN
C: HIRUGEN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,9916
Polymers35,4383
Non-polymers5533
Water2,414134
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)71.140, 72.260, 72.730
Angle α, β, γ (deg.)90.00, 100.70, 90.00
Int Tables number5
Space group name H-MC121

-
Components

-
Protein/peptide , 2 types, 2 molecules AC

#1: Protein/peptide THROMBIN


Mass: 4096.534 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: BLOOD / References: UniProt: P00734, thrombin
#3: Protein/peptide HIRUGEN


Mass: 1561.577 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hirudo medicinalis (medicinal leech) / References: UniProt: P01050*PLUS

-
Protein , 1 types, 1 molecules B

#2: Protein THROMBIN


Mass: 29780.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Tissue: BLOOD / References: UniProt: P00734, thrombin

-
Non-polymers , 3 types, 137 molecules

#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-0IV / 2-{(3S)-3-[(benzylsulfonyl)amino]-2-oxopiperidin-1-yl}-N-{(2S)-1-[(3R)-1-carbamimidoylpiperidin-3-yl]-3-oxopropan-2-yl}acetamide / CVS1694


Type: peptide-like, Peptide-like / Class: Inhibitor / Mass: 506.618 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H34N6O5S
References: N-(benzylsulfonyl)-L-norvalyl-N-{(1R)-2-[(3R)-1-carbamimidoylpiperidin-3-yl]-1-formylethyl}glycinamide
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 134 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY
Nonpolymer detailsTHE ACTIVE SITE INHIBITOR IS IN ITS R CHIRAL FORM. THE ACTIVE SITE SER 195 IS CLOSE TO THE CARBONYL ...THE ACTIVE SITE INHIBITOR IS IN ITS R CHIRAL FORM. THE ACTIVE SITE SER 195 IS CLOSE TO THE CARBONYL CARBON (C9) OF THE ALDEHYDE GROUP OF THE INHIBITOR BUT DOES NOT FORM A TETRAHEDRAL INTERMEDIATE

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 51 %
Crystal growpH: 7.5 / Details: pH 7.5
Crystal
*PLUS
Crystal grow
*PLUS
Method: unknown
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDChemical formula
128 %PEG800011
20.1 MTris11
30.2 Msodium acetate11
41 mM11NaN3
515 mMprotain12

-
Data collection

DiffractionMean temperature: 300 K
Diffraction sourceWavelength: 1.5418
DetectorType: RIGAKU / Detector: IMAGE PLATE / Date: Sep 15, 1995
RadiationMonochromator: NI FILTER / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionHighest resolution: 1.8 Å / Num. obs: 19592 / % possible obs: 86 % / Observed criterion σ(I): 1.5 / Redundancy: 2 % / Rmerge(I) obs: 0.059 / Rsym value: 0.12 / Net I/σ(I): 12.2
Reflection shellResolution: 2.1→2.4 Å / Redundancy: 2 % / Rmerge(I) obs: 0.13 / Mean I/σ(I) obs: 2.5 / Rsym value: 0.25 / % possible all: 39
Reflection
*PLUS
Highest resolution: 2.1 Å / Redundancy: 1.8 % / Num. measured all: 36756
Reflection shell
*PLUS
% possible obs: 39 % / Rmerge(I) obs: 0.137

-
Processing

Software
NameVersionClassification
R-AXISIIdata collection
R-AXISIIdata reduction
X-PLORmodel building
PROLSQrefinement
X-PLORrefinement
R-AXISIIdata scaling
X-PLORphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1TMB

1tmb


Resolution: 2.1→7 Å / σ(F): 4
RfactorNum. reflection% reflection
Rwork0.157 --
obs-17909 75 %
Displacement parametersBiso mean: 27.5 Å2
Refine analyzeLuzzati coordinate error obs: 0.2 Å / Luzzati d res low obs: 7 Å
Refinement stepCycle: LAST / Resolution: 2.1→7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2241 0 37 134 2412
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONp_bond_d0.0120.02
X-RAY DIFFRACTIONp_angle_d0.0420.03
X-RAY DIFFRACTIONp_angle_deg
X-RAY DIFFRACTIONp_planar_d0.0550.05
X-RAY DIFFRACTIONp_hb_or_metal_coord
X-RAY DIFFRACTIONp_mcbond_it1.11
X-RAY DIFFRACTIONp_mcangle_it1.81.5
X-RAY DIFFRACTIONp_scbond_it2.62
X-RAY DIFFRACTIONp_scangle_it3.82.5
X-RAY DIFFRACTIONp_plane_restr0.0270.03
X-RAY DIFFRACTIONp_chiral_restr0.150.2
X-RAY DIFFRACTIONp_singtor_nbd0.220.6
X-RAY DIFFRACTIONp_multtor_nbd0.310.6
X-RAY DIFFRACTIONp_xhyhbond_nbd
X-RAY DIFFRACTIONp_xyhbond_nbd0.280.6
X-RAY DIFFRACTIONp_planar_tor43
X-RAY DIFFRACTIONp_staggered_tor2015
X-RAY DIFFRACTIONp_orthonormal_tor
X-RAY DIFFRACTIONp_transverse_tor3020
X-RAY DIFFRACTIONp_special_tor
Software
*PLUS
Name: PROLSQ / Classification: refinement
Refinement
*PLUS
Rfactor obs: 0.17
Solvent computation
*PLUS
Displacement parameters
*PLUS
Biso mean: 29.2 Å2

+
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