[English] 日本語
Yorodumi
- PDB-7ppg: CRYSTAL STRUCTURE OF NAMPT IN COMPLEX WITH COMPOUND 9 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ppg
TitleCRYSTAL STRUCTURE OF NAMPT IN COMPLEX WITH COMPOUND 9
ComponentsNicotinamide phosphoribosyltransferase
KeywordsTRANSFERASE / SMALL MOLECULE INHIBITOR / NMPRTASE
Function / homology
Function and homology information


nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / NAD biosynthesis via nicotinamide riboside salvage pathway / Nicotinamide salvaging / NAD biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian gene expression / cytokine activity / circadian regulation of gene expression ...nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / NAD biosynthesis via nicotinamide riboside salvage pathway / Nicotinamide salvaging / NAD biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian gene expression / cytokine activity / circadian regulation of gene expression / cell junction / cell-cell signaling / nuclear speck / positive regulation of cell population proliferation / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular exosome / identical protein binding / cytosol
Similarity search - Function
Nicotinamide phosphoribosyl transferase / Nicotinamide phosphoribosyltransferase, N-terminal domain / Nicotinamide phosphoribosyltransferase, N-terminal domain / Nicotinate/nicotinamide phosphoribosyltransferase / Nicotinate phosphoribosyltransferase (NAPRTase) family / Nicotinate phosphoribosyltransferase-like, C-terminal / Aldolase-type TIM barrel
Similarity search - Domain/homology
Chem-7YX / PHOSPHATE ION / Nicotinamide phosphoribosyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.13 Å
AuthorsHillig, R.C.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Bioconjug.Chem. / Year: 2022
Title: A Novel NAMPT Inhibitor-Based Antibody-Drug Conjugate Payload Class for Cancer Therapy.
Authors: Bohnke, N. / Berger, M. / Griebenow, N. / Rottmann, A. / Erkelenz, M. / Hammer, S. / Berndt, S. / Gunther, J. / Wengner, A.M. / Stelte-Ludwig, B. / Mahlert, C. / Greven, S. / Dietz, L. / ...Authors: Bohnke, N. / Berger, M. / Griebenow, N. / Rottmann, A. / Erkelenz, M. / Hammer, S. / Berndt, S. / Gunther, J. / Wengner, A.M. / Stelte-Ludwig, B. / Mahlert, C. / Greven, S. / Dietz, L. / Jorissen, H. / Barak, N. / Bomer, U. / Hillig, R.C. / Eberspaecher, U. / Weiske, J. / Giese, A. / Mumberg, D. / Nising, C.F. / Weinmann, H. / Sommer, A.
History
DepositionSep 13, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 15, 2022Provider: repository / Type: Initial release
Revision 1.1Jun 22, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Nicotinamide phosphoribosyltransferase
B: Nicotinamide phosphoribosyltransferase
C: Nicotinamide phosphoribosyltransferase
D: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)225,19119
Polymers222,6084
Non-polymers2,58315
Water23,7081316
1
A: Nicotinamide phosphoribosyltransferase
B: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,61010
Polymers111,3042
Non-polymers1,3068
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area9940 Å2
ΔGint-51 kcal/mol
Surface area32330 Å2
MethodPISA
2
C: Nicotinamide phosphoribosyltransferase
D: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,5819
Polymers111,3042
Non-polymers1,2777
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area9770 Å2
ΔGint-67 kcal/mol
Surface area32300 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.956, 106.180, 121.340
Angle α, β, γ (deg.)90.000, 96.530, 90.000
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22C
13A
23D
14B
24C
15B
25D
16C
26D

NCS domain segments:

Component-ID: _ / Beg auth comp-ID: PHE / Beg label comp-ID: PHE / End auth comp-ID: ILE / End label comp-ID: ILE / Refine code: _ / Auth seq-ID: 9 - 484 / Label seq-ID: 10 - 485

Dom-IDEns-IDAuth asym-IDLabel asym-ID
11AA
21BB
12AA
22CC
13AA
23DD
14BB
24CC
15BB
25DD
16CC
26DD

NCS ensembles :
ID
1
2
3
4
5
6

-
Components

#1: Protein
Nicotinamide phosphoribosyltransferase / NAmPRTase / Nampt / Pre-B-cell colony-enhancing factor 1 / Pre-B cell-enhancing factor / Visfatin


Mass: 55651.988 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Details: N-terminal Gly is a cloning artifact, stems from TEV cleavage site
Source: (gene. exp.) Homo sapiens (human) / Gene: NAMPT, PBEF, PBEF1 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P43490, nicotinamide phosphoribosyltransferase
#2: Chemical
ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: PO4
#3: Chemical
ChemComp-7YX / N-[4-[(4R)-1-cyclopentyl-4-methyl-6-oxidanylidene-4,5-dihydropyridazin-3-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide


Mass: 417.503 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H27N5O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1316 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.39 Å3/Da / Density % sol: 48.43 %
Description: Crescent-shaped, plate-shaped crystals, often with very uneven surfaces
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.6
Details: 1 microliter of protein mixed with 1 microliter of reservoir buffer (27-31% PEG 3350 (w/v), 200 mM NaCl, 100 mM sodium dihydrogen phosphate pH 7.6) incubated for 5 min, then streak seeded ...Details: 1 microliter of protein mixed with 1 microliter of reservoir buffer (27-31% PEG 3350 (w/v), 200 mM NaCl, 100 mM sodium dihydrogen phosphate pH 7.6) incubated for 5 min, then streak seeded (with crystals obtained previously under identical conditions). Ligand added prior to crystallization (2 MILLIMOLAR FROM 100 MILLIMOLAR STOCK IN DMSO) and incubated for 1.5 h at 277 K. CRYO BUFFER consisted of RESERVOIR supplemented WITH 2 MILLIMOLAR INHIBITOR AND 15% ETHYLENGLYCOL

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.91841 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 28, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
ReflectionResolution: 2.13→48.59 Å / Num. obs: 114934 / % possible obs: 98 % / Redundancy: 2.67 % / Biso Wilson estimate: 24.9 Å2 / CC1/2: 0.994 / Rrim(I) all: 0.151 / Rsym value: 0.121 / Net I/σ(I): 6.89
Reflection shellResolution: 2.13→2.26 Å / Redundancy: 2.7 % / Mean I/σ(I) obs: 2.2 / Num. unique obs: 18131 / CC1/2: 0.854 / Rrim(I) all: 0.57 / Rsym value: 0.459 / % possible all: 96.1

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
PDB_EXTRACT3.27data extraction
XDSVERSION January 10, 2014data reduction
pointlessversion 1.9.12data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2GVJ

2gvj


Resolution: 2.13→48.59 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.897 / SU B: 8.165 / SU ML: 0.21 / SU R Cruickshank DPI: 0.3398 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.34 / ESU R Free: 0.256 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES: REFINED INDIVIDUALLY.
RfactorNum. reflection% reflectionSelection details
Rfree0.3025 5747 5 %RANDOM
Rwork0.2528 ---
obs0.2553 109187 97.97 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 155.16 Å2 / Biso mean: 20.514 Å2 / Biso min: 0.5 Å2
Baniso -1Baniso -2Baniso -3
1--0.76 Å2-0 Å2-0.65 Å2
2---0.2 Å20 Å2
3---1.08 Å2
Refinement stepCycle: final / Resolution: 2.13→48.59 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14937 0 175 1329 16441
Biso mean--24.7 25.74 -
Num. residues----1867
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.01315507
X-RAY DIFFRACTIONr_bond_other_d0.0020.01714654
X-RAY DIFFRACTIONr_angle_refined_deg1.4221.65721022
X-RAY DIFFRACTIONr_angle_other_deg1.2861.59733893
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.90751867
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.73523.842747
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.573152698
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.371552
X-RAY DIFFRACTIONr_chiral_restr0.0680.21968
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0217325
X-RAY DIFFRACTIONr_gen_planes_other0.0010.023439
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A153240.08
12B153240.08
21A154910.06
22C154910.06
31A152640.08
32D152640.08
41B153770.08
42C153770.08
51B154110.06
52D154110.06
61C152420.08
62D152420.08
LS refinement shellResolution: 2.13→2.182 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.342 401 -
Rwork0.318 7614 -
obs--92.77 %

+
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://pdbjlvh1.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