[English] 日本語
Yorodumi
- PDB-5kby: Crystal structure of dipeptidyl peptidase IV in complex with SYR-472 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5kby
TitleCrystal structure of dipeptidyl peptidase IV in complex with SYR-472
ComponentsDipeptidyl peptidase 4Dipeptidyl peptidase-4
KeywordsHYDROLASE/HYDROLASE INHIBITOR / peptidase / glp-1 / metabolic disease / co-complex / HYDROLASE-HYDROLASE 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-6RL / Dipeptidyl peptidase 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å
AuthorsSkene, R.J. / Jennings, A.J.
CitationJournal: Plos One / Year: 2016
Title: Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism.
Authors: Grimshaw, C.E. / Jennings, A. / Kamran, R. / Ueno, H. / Nishigaki, N. / Kosaka, T. / Tani, A. / Sano, H. / Kinugawa, Y. / Koumura, E. / Shi, L. / Takeuchi, K.
History
DepositionJun 3, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 13, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 7, 2016Group: Non-polymer description
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / 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 / pdbx_struct_oper_list / pdbx_validate_close_contact / 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 / _atom_site_anisotrop.id / _chem_comp.name / _chem_comp.type / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_oper_list.symmetry_operation / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_seq_id_1 / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Sep 27, 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)350,39829
Polymers343,1044
Non-polymers7,29425
Water28,7701597
1
A: Dipeptidyl peptidase 4
B: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)175,73416
Polymers171,5522
Non-polymers4,18214
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8540 Å2
ΔGint38 kcal/mol
Surface area59340 Å2
MethodPISA
2
C: Dipeptidyl peptidase 4
D: Dipeptidyl peptidase 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)174,66413
Polymers171,5522
Non-polymers3,11211
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7450 Å2
ΔGint21 kcal/mol
Surface area58290 Å2
MethodPISA
3
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)350,39829
Polymers343,1044
Non-polymers7,29425
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_656-x+1,y+1/2,-z+11
Buried area16620 Å2
ΔGint57 kcal/mol
Surface area116990 Å2
MethodPISA
Unit cell
Length a, b, c (Å)121.573, 122.165, 143.704
Angle α, β, γ (deg.)90.000, 114.570, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 85775.945 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DPP4, ADCP2, CD26 / Production host: unidentified baculovirus / 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.: 6
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: 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.: 15
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
#4: Chemical
ChemComp-6RL / 2-[[6-[(3~{R})-3-azanylpiperidin-1-yl]-3-methyl-2,4-bis(oxidanylidene)pyrimidin-1-yl]methyl]-4-fluoranyl-benzenecarboni trile / SYR-472 / Trelagliptin


Mass: 357.382 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H20FN5O2
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 1597 / 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: 2.85 Å3/Da / Density % sol: 56.83 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / Details: 22.2% PEG MME 2000, 0.1M Bicine pH 8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.987 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 11, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.987 Å / Relative weight: 1
ReflectionResolution: 2.25→50 Å / Num. obs: 178650 / % possible obs: 98.9 % / Redundancy: 4 % / Rmerge(I) obs: 0.083 / Χ2: 1.009 / Net I/av σ(I): 14.475 / Net I/σ(I): 9.5 / Num. measured all: 712558
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.25-2.32.90.541188.8
2.3-2.363.30.523195.8
2.36-2.423.70.478199.1
2.42-2.540.438199.9
2.5-2.584.10.3881100
2.58-2.674.20.3061100
2.67-2.774.20.2471100
2.77-2.94.20.1841100
2.9-3.054.20.141100
3.05-3.244.20.1051100
3.24-3.54.20.0861100
3.5-3.854.10.0721100
3.85-4.44.10.0541100
4.4-5.554.10.0391100
5.55-504.20.031199.9

-
Processing

Software
NameVersionClassification
REFMAC5.7.0025refinement
HKL-2000data collection
HKL-2000data scaling
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3G0B

3g0b


Resolution: 2.24→34.57 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.943 / SU B: 10.877 / SU ML: 0.143 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.251 / ESU R Free: 0.193 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.215 8950 5 %RANDOM
Rwork0.1743 ---
obs0.1764 169608 97.78 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 144.65 Å2 / Biso mean: 50.867 Å2 / Biso min: 19.67 Å2
Baniso -1Baniso -2Baniso -3
1--0.16 Å20 Å20 Å2
2--0.25 Å20 Å2
3----0.09 Å2
Refinement stepCycle: final / Resolution: 2.24→34.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms23764 0 482 1597 25843
Biso mean--65.64 46.22 -
Num. residues----2900
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.01925013
X-RAY DIFFRACTIONr_bond_other_d0.0020.0222439
X-RAY DIFFRACTIONr_angle_refined_deg1.2461.95234056
X-RAY DIFFRACTIONr_angle_other_deg0.7423.00251455
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.41152890
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.00623.9011228
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.866153974
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.48915120
X-RAY DIFFRACTIONr_chiral_restr0.0760.23629
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0228170
X-RAY DIFFRACTIONr_gen_planes_other0.0010.026128
LS refinement shellResolution: 2.243→2.301 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.306 520 -
Rwork0.278 9615 -
all-10135 -
obs--75.51 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.71210.1281-0.03540.15160.02920.2967-0.0229-0.0766-0.14440.0125-0.0025-0.0494-0.04850.06880.02540.05150.0151-0.01470.05750.020.093449.463831.999818.7043
20.97310.0704-0.18320.05570.01970.3068-0.044-0.0695-0.1415-0.01430.02880.003-0.0595-0.04140.01520.04630.02110.01290.05420.04240.0895-6.414225.197920.1457
31.16670.382-0.11430.47-0.33520.29140.1107-0.2665-0.0825-0.0027-0.2114-0.1301-0.02580.14320.10070.1217-0.0406-0.01730.11590.07170.068690.5409-29.103847.1054
41.35720.06390.25420.0394-0.03250.24770.0486-0.09820.114-0.0026-0.0097-0.0088-0.0152-0.1498-0.03890.08550.02620.01820.12840.05940.052535.853-28.526133.4098
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A40 - 766
2X-RAY DIFFRACTION2B36 - 766
3X-RAY DIFFRACTION3C40 - 766
4X-RAY DIFFRACTION4D40 - 766

+
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