[English] 日本語
Yorodumi
- PDB-4ffw: Crystal Structure of Dipeptidyl Peptidase IV (DPP4, DPP-IV, CD26)... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ffw
TitleCrystal Structure of Dipeptidyl Peptidase IV (DPP4, DPP-IV, CD26) in Complex with Fab + sitagliptin
Components
  • Dipeptidyl peptidase 4Dipeptidyl peptidase-4
  • Fab heavy chainFragment antigen-binding
  • Fab light chainFragment antigen-binding
KeywordsHYDROLASE/Immune System / INHIBITOR / hydrolase / HYDROLASE-Immune System / INHIBITOR complex
Function / homology
Function and homology information


B-1a B cell differentiation / regulation of T cell mediated immunity / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / positive regulation of natural killer cell mediated immunity / negative regulation of neutrophil chemotaxis / regulation of cell-cell adhesion mediated by integrin / negative regulation of extracellular matrix disassembly / psychomotor behavior / dipeptidyl-peptidase IV ...B-1a B cell differentiation / regulation of T cell mediated immunity / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / positive regulation of natural killer cell mediated immunity / negative regulation of neutrophil chemotaxis / regulation of cell-cell adhesion mediated by integrin / negative regulation of extracellular matrix disassembly / psychomotor behavior / dipeptidyl-peptidase IV / intercellular canaliculus / chemorepellent activity / dipeptidyl-peptidase activity / locomotory exploration behavior / lamellipodium membrane / endocytic vesicle / endothelial cell migration / behavioral fear response / aminopeptidase activity / collagen binding / T cell costimulation / T cell activation / serine-type peptidase activity / peptide binding / protein catabolic process / virus receptor activity / lamellipodium / protease binding / response to hypoxia / cell adhesion / membrane raft / apical plasma membrane / signaling receptor binding / serine-type endopeptidase activity / positive regulation of cell population proliferation / cell surface / protein homodimerization activity / proteolysis / extracellular region / identical protein binding / plasma membrane
Similarity search - Function
Dipeptidyl peptidase 4, low complexity region / Dipeptidyl peptidase IV (DPP IV) low complexity region / 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 ...Dipeptidyl peptidase 4, low complexity region / Dipeptidyl peptidase IV (DPP IV) low complexity region / 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 / Immunoglobulins / Immunoglobulin-like / Sandwich / Rossmann fold / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Chem-715 / Dipeptidyl peptidase 4
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Mus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsWang, Z. / Sudom, A. / Walker, N.P. / Min, X.
CitationJournal: To be published
Title: An Inhibitory Antibody Against DPP IV Improves Glucose Tolerance in vivo - Validation of Large Molecule Approach for DPP IV Inhibition
Authors: Tang, J. / Majeti, J. / Sudom, A. / Xiong, Y. / Lu, M. / Liu, Q. / Higbee, J. / Zhang, Y. / Wang, Y. / Wang, W. / Cao, P. / Xia, Z. / Johnstone, S. / Yang, X. / Yu, T. / Sharkov, N. / ...Authors: Tang, J. / Majeti, J. / Sudom, A. / Xiong, Y. / Lu, M. / Liu, Q. / Higbee, J. / Zhang, Y. / Wang, Y. / Wang, W. / Cao, P. / Xia, Z. / Johnstone, S. / Yang, X. / Yu, T. / Sharkov, N. / Walker, N. / Tu, H. / Shen, W. / Wang, Z.
History
DepositionJun 1, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 12, 2012Provider: repository / Type: Initial release
Revision 1.1Jun 6, 2018Group: Data collection / Category: diffrn_radiation_wavelength / diffrn_source / Item: _diffrn_source.pdbx_wavelength_list
Revision 1.2May 19, 2021Group: Derived calculations / Source and taxonomy / Structure summary
Category: chem_comp / entity ...chem_comp / entity / entity_src_gen / pdbx_entity_nonpoly / struct_site
Item: _chem_comp.name / _entity.pdbx_description ..._chem_comp.name / _entity.pdbx_description / _entity_src_gen.host_org_common_name / _entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_strain / _pdbx_entity_nonpoly.name / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dipeptidyl peptidase 4
B: Dipeptidyl peptidase 4
C: Fab light chain
D: Fab heavy chain
H: Fab heavy chain
L: Fab light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)261,8948
Polymers261,0806
Non-polymers8152
Water70339
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)97.770, 200.860, 97.930
Angle α, β, γ (deg.)90.00, 93.64, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Dipeptidyl peptidase 4 / Dipeptidyl peptidase-4 / Bile canaliculus domain-specific membrane glycoprotein / Dipeptidyl peptidase IV / DPP IV / GP110 ...Bile canaliculus domain-specific membrane glycoprotein / Dipeptidyl peptidase IV / DPP IV / GP110 glycoprotein / T-cell activation antigen CD26 / Dipeptidyl peptidase 4 membrane form / Dipeptidyl peptidase IV membrane form / Dipeptidyl peptidase 4 soluble form / Dipeptidyl peptidase IV soluble form / Dipeptidyl peptidase 4 60 kDa soluble form / Dipeptidyl peptidase IV 60 kDa soluble form


Mass: 84337.578 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Dpp4, Cd26 / Cell line (production host): HEK293 6E / Production host: Homo sapiens (human) / References: UniProt: P14740, dipeptidyl-peptidase IV
#2: Antibody Fab light chain / Fragment antigen-binding


Mass: 22895.209 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
#3: Antibody Fab heavy chain / Fragment antigen-binding


Mass: 23307.127 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
#4: Chemical ChemComp-715 / (2R)-4-OXO-4-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-1-(2,4,5-TRIFLUOROPHENYL)BUTAN-2-A MINE / Sitagliptin / Sitagliptin


Mass: 407.314 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H15F6N5O / Comment: medication*YM
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 39 / 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: 3.68 Å3/Da / Density % sol: 66.54 %
Crystal growTemperature: 289 K / Method: vapor diffusion / pH: 7.9
Details: 2.2-2.7 M ammonium sulfate, 0.1 M Tris 7.5-7.9, vapor diffusion, temperature 289K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 15, 2010 / Details: 3X3 CCD ARRAY
RadiationMonochromator: DOUBLE-CRYSTAL, SI (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.9→100.43 Å / Num. all: 82634 / Num. obs: 82634 / % possible obs: 99.2 % / Redundancy: 3.7 % / Rsym value: 0.08 / Net I/σ(I): 10.8
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsRsym valueDiffraction-ID% possible all
2.9-3.063.80.4221.70.422199.2
3.06-3.243.80.2492.90.249199.2
3.24-3.473.80.1534.60.153199.3
3.47-3.743.80.1016.40.101199.4
3.74-4.13.70.0797.90.079199.5
4.1-4.593.70.0629.60.062199.7
4.59-5.293.70.057100.057199.6
5.29-6.483.60.0619.60.061199.1
6.48-9.173.50.05111.10.051196.5
9.17-71.3533.80.0511.40.05199.5

-
Processing

Software
NameVersionClassificationNB
MOSFLMdata reduction
SCALA3.3.15data scaling
REFMACrefinement
PDB_EXTRACT3.11data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9→29.99 Å / Cor.coef. Fo:Fc: 0.88 / Cor.coef. Fo:Fc free: 0.86 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 22.094 / SU ML: 0.416 / SU R Cruickshank DPI: 1.4751 / Cross valid method: THROUGHOUT / ESU R: 1.566 / ESU R Free: 0.444 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.31094 4123 5 %RANDOM
Rwork0.28654 ---
obs0.28777 78420 99.09 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 93.533 Å2
Baniso -1Baniso -2Baniso -3
1--0.05 Å2-0 Å2-0.01 Å2
2--0.1 Å20 Å2
3----0.04 Å2
Refinement stepCycle: LAST / Resolution: 2.9→29.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms18171 0 56 39 18266
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.01918746
X-RAY DIFFRACTIONr_bond_other_d0.0010.0217019
X-RAY DIFFRACTIONr_angle_refined_deg0.7971.93825535
X-RAY DIFFRACTIONr_angle_other_deg0.6483.00239236
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.55652272
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.29524.196846
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.698153017
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.0521575
X-RAY DIFFRACTIONr_chiral_restr0.0480.22769
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.02121226
X-RAY DIFFRACTIONr_gen_planes_other0.0010.024461
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.7051.511528
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.35218720
X-RAY DIFFRACTIONr_scbond_it1.76237423
X-RAY DIFFRACTIONr_scangle_it3.0174.57097
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.9→2.975 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.424 300 -
Rwork0.386 5784 -
obs--99.22 %

+
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