[English] 日本語
Yorodumi
- PDB-8ivu: Crystal Structure of Human NAMPT in complex with A4276 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ivu
TitleCrystal Structure of Human NAMPT in complex with A4276
ComponentsNicotinamide phosphoribosyltransferase
KeywordsTRANSFERASE / NAMPT / Inhibitor / Complex / Cancer
Function / homology
Function and homology information


nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / : / Nicotinamide salvage / NAD+ biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian expression / cytokine activity / circadian regulation of gene expression / cell junction ...nicotinamide phosphoribosyltransferase / nicotinamide phosphoribosyltransferase activity / : / Nicotinamide salvage / NAD+ biosynthetic process / NPAS4 regulates expression of target genes / BMAL1:CLOCK,NPAS2 activates circadian expression / cytokine activity / circadian regulation of gene expression / cell junction / cell-cell signaling / positive regulation of canonical NF-kappaB signal transduction / positive regulation of ERK1 and ERK2 cascade / nuclear speck / inflammatory response / positive regulation of cell population proliferation / positive regulation of gene expression / 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
PHOSPHATE ION / Chem-SJ6 / Nicotinamide phosphoribosyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.09000922463 Å
AuthorsKang, B.G. / Cha, S.S.
Funding support Korea, Republic Of, 1items
OrganizationGrant numberCountry
National Research Foundation (NRF, Korea) Korea, Republic Of
CitationJournal: Theranostics / Year: 2023
Title: Discovery of a novel NAMPT inhibitor that selectively targets NAPRT-deficient EMT-subtype cancer cells and alleviates chemotherapy-induced peripheral neuropathy.
Authors: Kim, M. / Kim, H. / Kang, B.G. / Lee, J. / Kim, T. / Lee, H. / Jung, J. / Oh, M.J. / Seo, S. / Ryu, M.J. / Sung, Y. / Lee, Y. / Yeom, J. / Han, G. / Cha, S.S. / Jung, H. / Kim, H.S.
History
DepositionMar 28, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 11, 2023Provider: repository / Type: Initial release

-
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)224,89320
Polymers222,3804
Non-polymers2,51316
Water12,791710
1
A: Nicotinamide phosphoribosyltransferase
B: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,44610
Polymers111,1902
Non-polymers1,2578
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10020 Å2
ΔGint-82 kcal/mol
Surface area32420 Å2
MethodPISA
2
C: Nicotinamide phosphoribosyltransferase
D: Nicotinamide phosphoribosyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)112,44610
Polymers111,1902
Non-polymers1,2578
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10060 Å2
ΔGint-83 kcal/mol
Surface area32250 Å2
MethodPISA
Unit cell
Length a, b, c (Å)97.560, 116.690, 195.410
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-ID
11
21
31
41

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11GLUGLULYSLYSchain 'A'AA8 - 428 - 42
12LYSLYSASNASNchain 'A'AA53 - 48353 - 483
23GLUGLULYSLYSchain 'B'BB8 - 428 - 42
24LYSLYSASNASNchain 'B'BB53 - 48353 - 483
35GLUGLULYSLYSchain 'C'CC8 - 428 - 42
36LYSLYSASNASNchain 'C'CC53 - 48353 - 483
47GLUGLULYSLYSchain 'D'DD8 - 428 - 42
48LYSLYSASNASNchain 'D'DD53 - 48353 - 483

-
Components

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


Mass: 55594.938 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NAMPT, PBEF, PBEF1 / Production host: Escherichia coli B (bacteria)
References: UniProt: P43490, nicotinamide phosphoribosyltransferase
#2: Chemical
ChemComp-SJ6 / N-[[4-(6-methyl-1,3-benzoxazol-2-yl)phenyl]methyl]pyridine-3-carboxamide


Mass: 343.379 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H17N3O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: PO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 710 / 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: 2.47 Å3/Da / Density % sol: 50.16 %
Crystal growTemperature: 283.15 K / Method: microbatch / pH: 7
Details: 0.1M sodium phosphate pH 7.0, 0.2M sodium chloride, 25% (w/v) polyethylene glycol (PEG) 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PAL/PLS / Beamline: 5C (4A) / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jul 15, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.09→29.71 Å / Num. obs: 132238 / % possible obs: 99.9 % / Redundancy: 13.8 % / Biso Wilson estimate: 40.4049994066 Å2 / Rrim(I) all: 0.203 / Net I/σ(I): 8.8
Reflection shellResolution: 2.09→2.15 Å / Num. unique obs: 12302 / CC1/2: 0.594

-
Processing

Software
NameVersionClassification
Cootmodel building
PHENIX1.11.1-2575-000refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.09000922463→29.7083970676 Å / SU ML: 0.268400200344 / Cross valid method: NONE / σ(F): 1.34752066661 / Phase error: 25.7579814875
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.231333965665 6612 5.00075631523 %
Rwork0.20405167256 125608 -
obs0.205423269196 132220 99.9780716678 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 46.5320590098 Å2
Refinement stepCycle: LAST / Resolution: 2.09000922463→29.7083970676 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14920 0 164 710 15794
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0024866121668815436
X-RAY DIFFRACTIONf_angle_d0.58034821505320920
X-RAY DIFFRACTIONf_chiral_restr0.04400273587742268
X-RAY DIFFRACTIONf_plane_restr0.003603027475592648
X-RAY DIFFRACTIONf_dihedral_angle_d11.76974847649096
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.09001-2.11380.357788282122170.3009569691434138X-RAY DIFFRACTION99.9770431589
2.1138-2.13860.3410807206792170.3096250211754111X-RAY DIFFRACTION99.9538106236
2.1386-2.16470.3143557254162190.3018636765034161X-RAY DIFFRACTION99.9771741612
2.1647-2.19210.3030868784432170.2936652876614132X-RAY DIFFRACTION99.9310661765
2.1921-2.22090.3507765086952190.2884367358614146X-RAY DIFFRACTION99.9313186813
2.2209-2.25130.3016820910772190.2812903322744178X-RAY DIFFRACTION99.977262392
2.2513-2.28350.3213967338552160.2782026180764104X-RAY DIFFRACTION100
2.2835-2.31760.2780127612862210.2666807674094179X-RAY DIFFRACTION99.9772778914
2.3176-2.35380.2944093337962160.2553559557764105X-RAY DIFFRACTION100
2.3538-2.39230.2860544267452190.2612706633964169X-RAY DIFFRACTION100
2.3923-2.43360.3117725029642190.2657783970994161X-RAY DIFFRACTION100
2.4336-2.47780.2669126814092200.2572045515264184X-RAY DIFFRACTION100
2.4778-2.52540.3212969699622170.2528467419194121X-RAY DIFFRACTION100
2.5254-2.57690.27224171212210.2518021451034203X-RAY DIFFRACTION99.9774011299
2.5769-2.63290.3105215453272180.2474849636954145X-RAY DIFFRACTION100
2.6329-2.69410.2818952196052190.2451562882164158X-RAY DIFFRACTION100
2.6941-2.76150.256963350832190.2436864377214163X-RAY DIFFRACTION100
2.7615-2.83610.3295385665972200.2428443138164172X-RAY DIFFRACTION100
2.8361-2.91950.292781242722200.2515336483584188X-RAY DIFFRACTION100
2.9195-3.01360.2691052327462210.2378944425654187X-RAY DIFFRACTION99.97731912
3.0136-3.12120.2328056304982200.2217415559854177X-RAY DIFFRACTION100
3.1212-3.2460.2669473725182210.2239844470154204X-RAY DIFFRACTION100
3.246-3.39360.2505997173572200.2226749127114183X-RAY DIFFRACTION100
3.3936-3.57220.2284394495772210.2044240269134195X-RAY DIFFRACTION100
3.5722-3.79560.2216839025612230.188401156054241X-RAY DIFFRACTION100
3.7956-4.0880.1816418100352220.1660936625724210X-RAY DIFFRACTION99.9774419129
4.088-4.49810.1673569015062230.150408746194244X-RAY DIFFRACTION100
4.4981-5.14610.167012372642250.1421443907614275X-RAY DIFFRACTION99.977782715
5.1461-6.47240.180169196662270.166781144234310X-RAY DIFFRACTION100
6.4724-100.168541073142360.1520852220074464X-RAY DIFFRACTION99.7241671971

+
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