[English] 日本語
Yorodumi
- PDB-2iit: Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2iit
TitleHuman dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor
ComponentsDipeptidyl peptidase 4 soluble form
KeywordsHYDROLASE / ALPHA/BETA / BETA-PROPELLER / DIMER
Function / homology
Function and homology information


glucagon processing / negative regulation of neutrophil chemotaxis / regulation of cell-cell adhesion mediated by integrin / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / negative regulation of extracellular matrix disassembly / dipeptidyl-peptidase IV / chemorepellent activity / psychomotor behavior / intercellular canaliculus / dipeptidyl-peptidase activity ...glucagon processing / negative regulation of neutrophil chemotaxis / regulation of cell-cell adhesion mediated by integrin / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / negative regulation of extracellular matrix disassembly / dipeptidyl-peptidase IV / chemorepellent activity / psychomotor behavior / intercellular canaliculus / dipeptidyl-peptidase activity / peptide hormone processing / locomotory exploration behavior / lamellipodium membrane / endocytic vesicle / behavioral fear response / endothelial cell migration / aminopeptidase activity / receptor-mediated endocytosis of virus by host cell / T cell costimulation / serine-type peptidase activity / T cell activation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / lamellipodium / virus receptor activity / protease binding / membrane fusion / response to hypoxia / receptor-mediated virion attachment to host cell / cell adhesion / apical plasma membrane / membrane raft / symbiont entry into host cell / 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 / identical protein binding / membrane / plasma membrane
Similarity search - Function
Dipeptidylpeptidase IV, N-terminal domain / Prolyl endopeptidase family serine active site. / Peptidase S9, serine active site / : / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / 8 Propeller / Methanol Dehydrogenase; Chain A / Peptidase S9, prolyl oligopeptidase, catalytic domain / Prolyl oligopeptidase family ...Dipeptidylpeptidase IV, N-terminal domain / Prolyl endopeptidase family serine active site. / Peptidase S9, serine active site / : / Dipeptidylpeptidase IV, N-terminal domain / Dipeptidyl peptidase IV (DPP IV) N-terminal region / 8 Propeller / Methanol Dehydrogenase; Chain A / 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-872 / Dipeptidyl peptidase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.35 Å
AuthorsScapin, G. / Biftu, T. / Weber, A.E.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2007
Title: (3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Authors: Biftu, T. / Feng, D. / Qian, X. / Liang, G.B. / Kieczykowski, G. / Eiermann, G. / He, H. / Leiting, B. / Lyons, K. / Petrov, A. / Sinha-Roy, R. / Zhang, B. / Scapin, G. / Patel, S. / Gao, Y. ...Authors: Biftu, T. / Feng, D. / Qian, X. / Liang, G.B. / Kieczykowski, G. / Eiermann, G. / He, H. / Leiting, B. / Lyons, K. / Petrov, A. / Sinha-Roy, R. / Zhang, B. / Scapin, G. / Patel, S. / Gao, Y.D. / Singh, S. / Wu, J. / Zhang, X. / Thornberry, N.A. / Weber, A.E.
History
DepositionSep 28, 2006Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 28, 2006Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Non-polymer description / Version format compliance
Revision 1.3Oct 18, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / database_PDB_caveat / 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 / pdbx_struct_conn_angle / pdbx_validate_chiral / struct_asym / struct_conn / 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_struct_assembly_gen.asym_id_list / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _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_comp_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_comp_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Oct 20, 2021Group: Database references / Structure summary / Category: chem_comp / database_2 / struct_ref_seq_dif
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details
Revision 2.2Aug 30, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 2.3Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dipeptidyl peptidase 4 soluble form
B: Dipeptidyl peptidase 4 soluble form
hetero molecules


Theoretical massNumber of molelcules
Total (without water)174,94620
Polymers168,9532
Non-polymers5,99318
Water13,691760
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area12230 Å2
ΔGint62 kcal/mol
Surface area59970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)118.224, 125.197, 136.870
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Dipeptidyl peptidase 4 soluble form / E.C.3.4.14.5 / Dipeptidyl peptidase IV soluble form


Mass: 84476.648 Da / Num. of mol.: 2 / Fragment: EXTRACELLULAR DOMAIN (residues 39-766) / Mutation: Ser39Thr
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DPP4, ADCP2, CD26 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf21 / References: UniProt: P27487, dipeptidyl-peptidase IV

-
Sugars , 3 types, 15 molecules

#2: Polysaccharide 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAca1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,2,1/[a2122h-1b_1-5_2*NCC/3=O][a2122h-1a_1-5_2*NCC/3=O]/1-2/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][a-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: 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.: 7
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)][a-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#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


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 6
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

-
Non-polymers , 3 types, 763 molecules

#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Chemical ChemComp-872 / (3R)-4-[(3R)-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL)BUTANOYL]-3-(2,2,2-TRIFLUOROETHYL)-1,4-DIAZEPAN-2-ONE


Mass: 411.342 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H19F6N3O2
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 760 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3 Å3/Da / Density % sol: 58.95 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8
Details: PEG 4000, SODIUM ACETATE, TRIS, pH 8.00, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 32-ID / Wavelength: 1 / Wavelength: 1 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Feb 15, 2004
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.35→50 Å / Num. all: 84841 / Num. obs: 82041 / % possible obs: 96.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.13 % / Biso Wilson estimate: 39.9 Å2 / Rmerge(I) obs: 0.085 / Net I/σ(I): 7.4
Reflection shellResolution: 2.35→2.43 Å / Redundancy: 5.03 % / Rmerge(I) obs: 0.44 / Mean I/σ(I) obs: 1.3 / Num. unique all: 8371 / % possible all: 92.5

-
Processing

Software
NameVersionClassificationNB
CNSrefinement
PDB_EXTRACT2data extraction
MAR345345DTBdata collection
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing
CNXrefinement
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1X70

1x70


Resolution: 2.35→30 Å / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.228 4134 4.9 %RANDOM
Rwork0.188 ---
obs0.19 81944 96.4 %-
all-85050 --
Solvent computationSolvent model: MASK / Bsol: 25.8 Å2 / ksol: 0.329 e/Å3
Displacement parametersBiso mean: 31.5 Å2
Baniso -1Baniso -2Baniso -3
1-6.841 Å20 Å20 Å2
2---1.076 Å20 Å2
3----5.405 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.31 Å0.25 Å
Luzzati d res low-5 Å
Luzzati sigma a0.32 Å0.25 Å
Refinement stepCycle: LAST / Resolution: 2.35→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms11930 0 393 760 13083
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.009
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_deg1.43
X-RAY DIFFRACTIONc_dihedral_angle_d24.6
X-RAY DIFFRACTIONc_improper_angle_d0.825
X-RAY DIFFRACTIONc_mcbond_it1.11.5
X-RAY DIFFRACTIONc_mcangle_it1.82
X-RAY DIFFRACTIONc_scbond_it1.82
X-RAY DIFFRACTIONc_scangle_it2.72.5
LS refinement shellResolution: 2.35→2.43 Å / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.315 356 4.3 %
Rwork0.272 7115 -
obs-7471 89.3 %

+
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