[English] 日本語
Yorodumi
- PDB-4n9b: Fragment-based Design of 3-Aminopyridine-derived Amides as Potent... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4n9b
TitleFragment-based Design of 3-Aminopyridine-derived Amides as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)
ComponentsNicotinamide phosphoribosyltransferase
Keywordstransferase/transferase inhibitor / transferase-transferase inhibitor complex
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 class I / Aldolase-type TIM barrel / TIM Barrel / Alpha-Beta Barrel / Alpha Beta
Similarity search - Domain/homology
Chem-2HH / PHOSPHATE ION / Nicotinamide phosphoribosyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.859 Å
AuthorsDragovich, P.S. / Zhao, G. / Baumeister, T. / Bravo, B. / Giannetti, A.M. / Ho, Y. / Hua, R. / Li, G. / Liang, X. / O'Brien, T. ...Dragovich, P.S. / Zhao, G. / Baumeister, T. / Bravo, B. / Giannetti, A.M. / Ho, Y. / Hua, R. / Li, G. / Liang, X. / O'Brien, T. / Skelton, N.J. / Wang, C. / Zhai, Q. / Oh, A. / Wang, W. / Wang, Y. / Xiao, Y. / Yuen, P. / Zak, M. / Zheng, X.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2014
Title: Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).
Authors: Dragovich, P.S. / Zhao, G. / Baumeister, T. / Bravo, B. / Giannetti, A.M. / Ho, Y.C. / Hua, R. / Li, G. / Liang, X. / Ma, X. / O'Brien, T. / Oh, A. / Skelton, N.J. / Wang, C. / Wang, W. / ...Authors: Dragovich, P.S. / Zhao, G. / Baumeister, T. / Bravo, B. / Giannetti, A.M. / Ho, Y.C. / Hua, R. / Li, G. / Liang, X. / Ma, X. / O'Brien, T. / Oh, A. / Skelton, N.J. / Wang, C. / Wang, W. / Wang, Y. / Xiao, Y. / Yuen, P.W. / Zak, M. / Zhao, Q. / Zheng, X.
History
DepositionOct 20, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 19, 2014Provider: repository / Type: Initial release
Revision 1.1Jul 17, 2019Group: Data collection / Refinement description / Category: software
Item: _software.classification / _software.name / _software.version
Revision 1.2Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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: Nicotinamide phosphoribosyltransferase
B: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)114,4796
Polymers113,8852
Non-polymers5944
Water1448
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8900 Å2
ΔGint-56 kcal/mol
Surface area33070 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.132, 106.313, 83.264
Angle α, β, γ (deg.)90.00, 96.27, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 56942.375 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NAMPT, PBEF, PBEF1 / Production host: Escherichia coli (E. coli)
References: UniProt: P43490, nicotinamide phosphoribosyltransferase
#2: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#3: Chemical ChemComp-2HH / 1-methyl-N-(pyridin-3-yl)-1H-pyrazole-5-carboxamide


Mass: 202.213 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H10N4O
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 8 / 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: 2.32 Å3/Da / Density % sol: 47.05 %
Crystal growTemperature: 292 K / Method: vapor diffusion, hanging drop / pH: 8.6
Details: crystals were grown from 0.2uL + 0.2uL drops containing 6mg/mL Nampt, 0.1M Sodium phosphate, 25-29% polyethylene glycol 3350, 0.2M NaCl, 1mM compound, pH 8.6, VAPOR DIFFUSION, HANGING DROP, temperature 292K

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.977408 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 5, 2012
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.977408 Å / Relative weight: 1
ReflectionResolution: 2.85→50 Å / Num. all: 24001 / Num. obs: 24001 / % possible obs: 100 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2
Reflection shellResolution: 2.85→2.95 Å / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.7.3_928refinement
PHASERphasing
REFMAC5.5.0110refinement
DENZOdata reduction
SCALEPACKdata scaling
HKL-2000data collection
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3DHF

3dhf


Resolution: 2.859→46.126 Å / Cor.coef. Fo:Fc: 0.846 / Cor.coef. Fo:Fc free: 0.817 / SU ML: 0.4 / σ(F): 0 / Phase error: 27.99 / Stereochemistry target values: ML / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflection
Rfree0.2844 1224 5.12 %
Rwork0.2339 --
obs0.2365 23903 98.92 %
all-24001 -
Solvent computationShrinkage radii: 0.86 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 0 Å2 / ksol: 0.315 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1-6.5767 Å2-0 Å21.2129 Å2
2--4.3311 Å20 Å2
3---2.2427 Å2
Refinement stepCycle: LAST / Resolution: 2.859→46.126 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7510 0 40 8 7558
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0027726
X-RAY DIFFRACTIONf_angle_d0.58510466
X-RAY DIFFRACTIONf_dihedral_angle_d11.0972844
X-RAY DIFFRACTIONf_chiral_restr0.0411144
X-RAY DIFFRACTIONf_plane_restr0.0031330
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8592-2.97370.31741430.22672332X-RAY DIFFRACTION93
2.9737-3.1090.29141440.20862506X-RAY DIFFRACTION100
3.109-3.27290.29761320.22852557X-RAY DIFFRACTION100
3.2729-3.47790.29121300.242533X-RAY DIFFRACTION100
3.4779-3.74630.29071450.23752528X-RAY DIFFRACTION100
3.7463-4.12310.27791220.22972530X-RAY DIFFRACTION100
4.1231-4.71920.2691380.21632544X-RAY DIFFRACTION99
4.7192-5.94370.26551280.24292575X-RAY DIFFRACTION100
5.9437-46.13180.28671420.25812574X-RAY DIFFRACTION99

+
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