[English] 日本語
Yorodumi
- PDB-3o9v: Crystal Structure of Human DPP4 Bound to TAK-986 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3o9v
TitleCrystal Structure of Human DPP4 Bound to TAK-986
ComponentsDipeptidyl peptidase 4Dipeptidyl peptidase-4
KeywordsHYDROLASE / SIGNALING PROTEIN/INHIBITOR / protease and 8-bladed beta-propeller domain / Aminopeptidase / Cell membrane / Glycoprotein / Membrane / Protease / Secreted / Serine protease / Signal-anchor / Transmembrane / SIGNALING PROTEIN / SIGNALING PROTEIN-INHIBITOR complex
Function / homology
Function and homology information


glucagon processing / negative regulation of neutrophil chemotaxis / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / regulation of cell-cell adhesion mediated by integrin / negative regulation of extracellular matrix disassembly / dipeptidyl-peptidase IV / psychomotor behavior / chemorepellent activity / intercellular canaliculus / dipeptidyl-peptidase activity ...glucagon processing / negative regulation of neutrophil chemotaxis / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / regulation of cell-cell adhesion mediated by integrin / negative regulation of extracellular matrix disassembly / dipeptidyl-peptidase IV / psychomotor behavior / chemorepellent activity / intercellular canaliculus / dipeptidyl-peptidase activity / peptide hormone processing / locomotory exploration behavior / lamellipodium membrane / endocytic vesicle / endothelial cell migration / behavioral fear response / aminopeptidase activity / T cell costimulation / serine-type peptidase activity / T cell activation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / virus receptor activity / lamellipodium / protease binding / receptor-mediated endocytosis of virus by host cell / membrane fusion / receptor-mediated virion attachment to host cell / response to hypoxia / cell adhesion / symbiont entry into host cell / membrane raft / apical plasma membrane / lysosomal membrane / signaling receptor binding / serine-type endopeptidase activity / focal adhesion / positive regulation of cell population proliferation / cell surface / protein homodimerization activity / proteolysis / extracellular exosome / extracellular region / membrane / identical protein binding / plasma membrane
Similarity search - Function
Dipeptidylpeptidase IV, N-terminal domain / 8 Propeller / Methanol Dehydrogenase; Chain A / Prolyl endopeptidase family serine active site. / Peptidase S9, serine active site / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / Peptidase S9, prolyl oligopeptidase, catalytic domain / Prolyl oligopeptidase family / Alpha/Beta hydrolase fold, catalytic domain ...Dipeptidylpeptidase IV, N-terminal domain / 8 Propeller / Methanol Dehydrogenase; Chain A / Prolyl endopeptidase family serine active site. / Peptidase S9, serine active site / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / Peptidase S9, prolyl oligopeptidase, catalytic domain / Prolyl oligopeptidase family / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / Rossmann fold / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Chem-10T / Dipeptidyl peptidase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.75 Å
AuthorsYano, J.K. / Aertgeerts, K.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Discovery of a 3-Pyridylacetic Acid Derivative (TAK-100) as a Potent, Selective and Orally Active Dipeptidyl Peptidase IV (DPP-4) Inhibitor.
Authors: Miyamoto, Y. / Banno, Y. / Yamashita, T. / Fujimoto, T. / Oi, S. / Moritoh, Y. / Asakawa, T. / Kataoka, O. / Yashiro, H. / Takeuchi, K. / Suzuki, N. / Ikedo, K. / Kosaka, T. / Tsubotani, S. ...Authors: Miyamoto, Y. / Banno, Y. / Yamashita, T. / Fujimoto, T. / Oi, S. / Moritoh, Y. / Asakawa, T. / Kataoka, O. / Yashiro, H. / Takeuchi, K. / Suzuki, N. / Ikedo, K. / Kosaka, T. / Tsubotani, S. / Tani, A. / Sasaki, M. / Funami, M. / Amano, M. / Yamamoto, Y. / Aertgeerts, K. / Yano, J. / Maezaki, H.
History
DepositionAug 4, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 9, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 8, 2014Group: Database references
Revision 1.3Nov 8, 2017Group: Refinement description / Category: software
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Database references / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_ref_seq_dif / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _chem_comp.type / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _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.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_ref_seq_dif.details
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Sep 6, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dipeptidyl peptidase 4
B: Dipeptidyl peptidase 4
C: Dipeptidyl peptidase 4
D: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)348,68723
Polymers343,1044
Non-polymers5,58419
Water8,125451
1
A: Dipeptidyl peptidase 4
B: Dipeptidyl peptidase 4
hetero molecules

C: Dipeptidyl peptidase 4
D: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)348,68723
Polymers343,1044
Non-polymers5,58419
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_656-x+1,y+1/2,-z+11
Buried area15580 Å2
ΔGint50 kcal/mol
Surface area120160 Å2
MethodPISA
2
A: Dipeptidyl peptidase 4
B: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)174,77713
Polymers171,5522
Non-polymers3,22511
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7800 Å2
ΔGint29 kcal/mol
Surface area60560 Å2
MethodPISA
3
C: Dipeptidyl peptidase 4
D: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)173,91010
Polymers171,5522
Non-polymers2,3588
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7140 Å2
ΔGint19 kcal/mol
Surface area60240 Å2
MethodPISA
Unit cell
Length a, b, c (Å)122.166, 122.886, 144.909
Angle α, β, γ (deg.)90.00, 114.59, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
Dipeptidyl peptidase 4 / Dipeptidyl peptidase-4 / Dipeptidyl peptidase IV / DPP IV / T-cell activation antigen CD26 / TP103 / Adenosine deaminase ...Dipeptidyl peptidase IV / DPP IV / T-cell activation antigen CD26 / TP103 / Adenosine deaminase complexing protein 2 / ADCP-2 / ADABP


Mass: 85775.945 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ADCP2, CD26, DPP4 / Plasmid: pFASTBAC / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27487, dipeptidyl-peptidase IV
#2: 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.: 5
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam 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
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: Chemical
ChemComp-10T / 5-(aminomethyl)-2-methyl-4-(4-methylphenyl)-6-(2-methylpropyl)pyridine-3-carboxic acid / TAK-986


Mass: 312.406 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C19H24N2O2
#4: 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 / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 10
Source method: isolated from a genetically manipulated source
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
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 451 / 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: 2.88 Å3/Da / Density % sol: 57.33 %
Crystal growTemperature: 277 K / Method: sitting drop, vapor diffusion
Details: 20% PEG MME 2000, 100 mM Bicine, pH 8-8.5, sitting drop, vapor diffusion, temperature 277K
PH range: 8-8.5

-
Data collection

DiffractionMean temperature: 92 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 10, 2007
RadiationMonochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.75→50 Å / Num. all: 101631 / Num. obs: 100525 / % possible obs: 98.9 % / Redundancy: 3.2 % / Rmerge(I) obs: 0.087 / Net I/σ(I): 9.6
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.75-2.82.90.514198.6
2.8-2.853.10.458198.8
2.85-2.93.10.393198.7
2.9-2.963.20.339198.8
2.96-3.033.20.289198.9
3.03-3.13.20.237198.9
3.1-3.173.20.198199.1
3.17-3.263.20.171199
3.26-3.363.20.141199.1
3.36-3.463.10.16197.7
3.46-3.593.20.117199
3.59-3.733.10.118198.1
3.73-3.93.10.094198.2
3.9-4.113.10.072198.8
4.11-4.363.20.054199.4
4.36-4.73.20.043199.5
4.7-5.173.10.041199.6
5.17-5.923.10.042199.6
5.92-7.463.20.042199.7
7.46-503.20.03199.4

-
Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation2.93 Å48.5 Å
Translation2.93 Å48.5 Å

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACT3.1data extraction
HKL-2000data collection
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdb entry 1R9M

1r9m


Resolution: 2.75→35 Å / Cor.coef. Fo:Fc: 0.924 / Cor.coef. Fo:Fc free: 0.883 / Occupancy max: 1 / Occupancy min: 1 / SU B: 27.288 / SU ML: 0.279 / Cross valid method: THROUGHOUT / ESU R Free: 0.371 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25961 5026 5 %RANDOM
Rwork0.20338 ---
obs0.20619 95320 98.65 %-
all-101701 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 41.346 Å2
Baniso -1Baniso -2Baniso -3
1--1.08 Å20 Å20.04 Å2
2--0.97 Å20 Å2
3---0.14 Å2
Refinement stepCycle: LAST / Resolution: 2.75→35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms23879 0 372 451 24702
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.02224988
X-RAY DIFFRACTIONr_bond_other_d0.0020.0216632
X-RAY DIFFRACTIONr_angle_refined_deg1.2221.94634021
X-RAY DIFFRACTIONr_angle_other_deg0.8753.00240156
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.34952910
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.26723.941236
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.821153988
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.15515120
X-RAY DIFFRACTIONr_chiral_restr0.0720.23606
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0227624
X-RAY DIFFRACTIONr_gen_planes_other0.0010.025376
X-RAY DIFFRACTIONr_nbd_refined0.20.24925
X-RAY DIFFRACTIONr_nbd_other0.2030.217046
X-RAY DIFFRACTIONr_nbtor_refined0.190.211980
X-RAY DIFFRACTIONr_nbtor_other0.0950.213174
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1480.2797
X-RAY DIFFRACTIONr_xyhbond_nbd_other0.10.21
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.180.221
X-RAY DIFFRACTIONr_symmetry_vdw_other0.270.241
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1990.27
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.3971.514865
X-RAY DIFFRACTIONr_mcbond_other0.0611.55876
X-RAY DIFFRACTIONr_mcangle_it0.684223545
X-RAY DIFFRACTIONr_scbond_it0.925311941
X-RAY DIFFRACTIONr_scangle_it1.4954.510476
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.745→2.816 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.372 355 -
Rwork0.305 6763 -
obs--96.11 %

+
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