[English] 日本語
Yorodumi
- PDB-6chh: Structure of human NNMT in complex with bisubstrate inhibitor MS2756 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6chh
TitleStructure of human NNMT in complex with bisubstrate inhibitor MS2756
ComponentsNicotinamide N-methyltransferase
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / protein-small molecule bisubstrate inhibitor complex / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


pyridine N-methyltransferase activity / nicotinamide N-methyltransferase / nicotinamide metabolic process / nicotinamide N-methyltransferase activity / Metabolism of ingested SeMet, Sec, MeSec into H2Se / positive regulation of protein deacetylation / NAD biosynthesis via nicotinamide riboside salvage pathway / Methylation / Nicotinamide salvaging / animal organ regeneration ...pyridine N-methyltransferase activity / nicotinamide N-methyltransferase / nicotinamide metabolic process / nicotinamide N-methyltransferase activity / Metabolism of ingested SeMet, Sec, MeSec into H2Se / positive regulation of protein deacetylation / NAD biosynthesis via nicotinamide riboside salvage pathway / Methylation / Nicotinamide salvaging / animal organ regeneration / positive regulation of gluconeogenesis / response to organonitrogen compound / methylation / response to xenobiotic stimulus / cytosol
Similarity search - Function
Methyltransferase, NNMT/PNMT/TEMT / Methyltransferase NNMT/PNMT/TEMT, conserved site / NNMT/PNMT/TEMT family / NNMT/PNMT/TEMT family of methyltransferases signature. / SAM-dependent methyltransferase NNMT/PNMT/TEMT-type profile. / Vaccinia Virus protein VP39 / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-F0P / Nicotinamide N-methyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsBabault, N. / Liu, J. / Jin, J.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM122749 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA218600 United States
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)R01HD088626 United States
CitationJournal: J. Med. Chem. / Year: 2018
Title: Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).
Authors: Babault, N. / Allali-Hassani, A. / Li, F. / Fan, J. / Yue, A. / Ju, K. / Liu, F. / Vedadi, M. / Liu, J. / Jin, J.
History
DepositionFeb 22, 2018Deposition site: RCSB / Processing site: RCSB
SupersessionJun 13, 2018ID: 6B1A
Revision 1.0Jun 13, 2018Provider: repository / Type: Initial release
Revision 1.1Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Apr 27, 2022Group: Database references / Category: database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Oct 4, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Nicotinamide N-methyltransferase
B: Nicotinamide N-methyltransferase
C: Nicotinamide N-methyltransferase
D: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)128,10310
Polymers125,8644
Non-polymers2,2386
Water4,071226
1
A: Nicotinamide N-methyltransferase
C: Nicotinamide N-methyltransferase
D: Nicotinamide N-methyltransferase
hetero molecules

B: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)128,10310
Polymers125,8644
Non-polymers2,2386
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_545x,y-1,z1
Buried area5150 Å2
ΔGint-23 kcal/mol
Surface area39940 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.440, 62.560, 107.979
Angle α, β, γ (deg.)91.760, 98.050, 111.830
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein
Nicotinamide N-methyltransferase /


Mass: 31466.033 Da / Num. of mol.: 4 / Mutation: K100A, E101A, E103A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NNMT / Plasmid: pET28a-LIC / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): RIL
References: UniProt: P40261, nicotinamide N-methyltransferase
#2: Chemical
ChemComp-F0P / (2~{S})-5-[2-(3-aminocarbonylphenyl)ethyl-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl]amino]-2-azanyl-pentanoic acid


Mass: 528.561 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H32N8O6
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 226 / 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: 2.28 Å3/Da / Density % sol: 46.09 %
Crystal growTemperature: 290.15 K / Method: vapor diffusion, hanging drop / pH: 7.2 / Details: 1.5 ammonium sulfate, 0.1 M HEPES pH 7.2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9792 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 19, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.3→106.481 Å / Num. all: 44070 / Num. obs: 44070 / % possible obs: 89.1 % / Redundancy: 3.3 % / Biso Wilson estimate: 20.97 Å2 / Rpim(I) all: 0.088 / Rrim(I) all: 0.167 / Rsym value: 0.141 / Net I/av σ(I): 4.1 / Net I/σ(I): 7.9 / Num. measured all: 147482
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
2.3-2.423.30.5830.966140.3650.6890.58391.6
2.42-2.573.30.4181.462120.2630.4940.41890.9
2.57-2.753.30.2882.158170.1810.3410.28890
2.75-2.973.30.2122.951540.1340.2520.21286.9
2.97-3.253.20.1384.543520.090.1660.13879.1
3.25-3.643.50.0976.646620.060.1140.09793.6
3.64-4.23.50.0797.940900.0490.0930.07993.1
4.2-5.143.40.0728.233560.0450.0850.07290.8
5.14-7.273.30.0827.223200.0530.0980.08281.6
7.27-53.243.40.0696.814930.0440.0820.06995.4

-
Processing

Software
NameVersionClassification
SCALA3.3.22data scaling
PHENIX1.13_2998refinement
PDB_EXTRACT3.24data extraction
PHASERphasing
iMOSFLMdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2IIP

2iip


Resolution: 2.3→53.24 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.98 / Phase error: 23.81
RfactorNum. reflection% reflection
Rfree0.2289 2037 4.62 %
Rwork0.1677 --
obs0.1705 44056 89.12 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 119.75 Å2 / Biso mean: 28.47 Å2 / Biso min: 5 Å2
Refinement stepCycle: final / Resolution: 2.3→53.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7971 0 160 226 8357
Biso mean--21.28 27.49 -
Num. residues----1023
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.3-2.35350.31161320.20072854298692
2.3535-2.41240.27871330.19142916304991
2.4124-2.47760.27371430.18272855299891
2.4776-2.55050.26661580.1852817297591
2.5505-2.63280.26271490.17242863301291
2.6328-2.72690.23971300.17332849297989
2.7269-2.83610.2581440.16982767291189
2.8361-2.96520.24791340.17332653278786
2.9652-3.12150.23821260.17072597272382
3.1215-3.3170.24881360.17962527266380
3.317-3.57310.2221330.16072933306694
3.5731-3.93260.2081390.1532964310394
3.9326-4.50140.17951520.14672897304993
4.5014-5.67020.19361150.15452765288087
5.6702-53.25450.20861130.17822762287588
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)
10.25120.6210.44492.81362.17832.0566-0.16560.25470.0604-0.46590.12980.0724-0.55730.02670.02670.23330.0099-0.03490.17860.03320.1379-4.67782.5076-19.7148
21.71260.0060.25871.1067-0.4392.0820.1691-0.17850.04570.0917-0.00430.3652-0.0552-0.2828-0.09840.0772-0.02480.00820.169-0.02510.1669-10.54852.07933.752
31.3159-0.1774-0.5370.93650.1790.80.1111-0.15030.0550.1665-0.1289-0.08040.04510.03480.03470.1415-0.037-0.02570.11930.020.15824.51563.23155.9901
41.43550.3373-0.20341.45340.3641.44230.1163-0.13810.32580.2079-0.05290.0936-0.3989-0.16760.05970.1862-0.009-0.00340.1151-0.01570.2034-4.358711.98686.956
51.00730.00370.00830.7256-0.39480.46320.09510.06920.02640.0261-0.1032-0.1922-0.02210.1524-0.00240.068-0.0214-0.02780.11850.02490.16887.4661-0.1998-0.9878
61.09240.27570.0210.8695-0.17261.1890.07310.1142-0.1139-0.2133-0.06440.06870.2024-0.0598-0.01210.04860.0147-0.02720.08580.01670.1641-3.779-9.6397-3.9407
70.3846-0.5319-0.38182.46951.40742.2385-0.1653-0.2683-0.03180.60.16380.14320.42210.0933-0.02660.1931-0.02540.04210.1570.01750.2275-27.967819.4436-4.4035
81.98940.1935-0.21360.6262-0.11261.77330.18130.157-0.0822-0.0733-0.12780.29440.0169-0.1578-0.04050.13780.05120.01910.1234-0.05380.1884-32.940820.2102-27.7513
91.5972-0.00870.68171.10150.05931.25120.06120.22480.0595-0.0689-0.0687-0.0984-0.09260.0532-0.01920.1130.020.03340.1309-0.00260.1896-18.492518.8281-30.0365
101.1823-0.32690.2741.5906-0.05621.25190.0570.1257-0.1022-0.2545-0.15480.10620.5405-0.17960.08880.1962-0.0197-0.00460.1592-0.02430.2079-27.404710.0076-31.1993
110.99810.28550.32631.35880.60011.90950.06140.0238-0.2046-0.21590.0408-0.19020.10340.1985-0.03060.11790.02230.00270.097-0.01040.199-16.217713.8401-26.3691
121.4373-0.3444-0.39430.6437-0.08721.05890.1064-0.02490.12730.1549-0.1102-0.08750.00050.0556-0.00020.0633-0.00650.02780.09430.02030.2045-20.549826.7726-18.3113
132.0490.5104-0.0780.7591-0.06981.43180.0663-0.20770.15170.0583-0.0262-0.1024-0.3072-0.0312-0.0090.0672-0.01430.01060.08570.00830.2536-24.533234.2885-23.7057
142.2238-0.17970.45971.99320.05161.40950.09440.2595-0.2091-0.3879-0.00750.04450.25460.1464-0.0770.27790.0664-0.02280.2055-0.03340.1296-9.0189-16.2611-48.7026
150.9736-0.1799-0.00620.64910.06552.1253-0.11840.3345-0.2328-0.5470.0504-0.05520.22290.0976-0.2030.53240.1411-0.05820.36-0.0997-0.013-8.1047-18.0511-57.9018
160.81920.06280.23370.91930.00251.10330.06260.0432-0.0206-0.1531-0.04910.2099-0.0621-0.12010.00530.18340.0344-0.04280.1951-0.03220.1403-18.7074-10.2145-44.3342
172.1269-0.1595-0.04891.4691-0.25111.28370.04610.03980.0795-0.0197-0.077-0.0877-0.06440.08920.03180.0858-0.0077-0.02130.13510.03370.1153-6.1214-8.9258-35.7564
182.2871-1.2868-0.48781.9021-0.48053.3938-0.0039-0.59160.13190.18970.0352-0.3361-0.01860.61690.24290.4117-0.0326-0.16480.34160.03830.11450.6288-26.467229.9561
191.1128-0.0727-0.28120.89920.01031.02720.1162-0.19030.20620.4578-0.05940.1211-0.25330.1205-0.01260.3286-0.08060.03710.2151-0.02630.1276-11.1375-17.707727.3093
200.6812-0.11020.00260.90720.04321.0432-0.0285-0.09270.01490.311-0.02750.33330.0085-0.08810.0090.1821-0.03970.0370.1681-0.01160.1426-19.1088-25.75120.1056
211.98750.16020.10191.4661-0.05361.26450.03880.0293-0.091-0.0891-0.038-0.15830.11290.12980.01440.08180.00550.03040.11640.02280.1427-6.3796-27.044911.7853
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid -8 through 16 )A-8 - 16
2X-RAY DIFFRACTION2chain 'A' and (resid 17 through 50 )A17 - 50
3X-RAY DIFFRACTION3chain 'A' and (resid 51 through 87 )A51 - 87
4X-RAY DIFFRACTION4chain 'A' and (resid 88 through 123 )A88 - 123
5X-RAY DIFFRACTION5chain 'A' and (resid 124 through 198 )A124 - 198
6X-RAY DIFFRACTION6chain 'A' and (resid 199 through 262 )A199 - 262
7X-RAY DIFFRACTION7chain 'B' and (resid -8 through 16 )B-8 - 16
8X-RAY DIFFRACTION8chain 'B' and (resid 17 through 50 )B17 - 50
9X-RAY DIFFRACTION9chain 'B' and (resid 51 through 87 )B51 - 87
10X-RAY DIFFRACTION10chain 'B' and (resid 88 through 123 )B88 - 123
11X-RAY DIFFRACTION11chain 'B' and (resid 124 through 150 )B124 - 150
12X-RAY DIFFRACTION12chain 'B' and (resid 151 through 217 )B151 - 217
13X-RAY DIFFRACTION13chain 'B' and (resid 218 through 262 )B218 - 262
14X-RAY DIFFRACTION14chain 'C' and (resid 16 through 87 )C16 - 87
15X-RAY DIFFRACTION15chain 'C' and (resid 88 through 123 )C88 - 123
16X-RAY DIFFRACTION16chain 'C' and (resid 124 through 198 )C124 - 198
17X-RAY DIFFRACTION17chain 'C' and (resid 199 through 261 )C199 - 261
18X-RAY DIFFRACTION18chain 'D' and (resid 16 through 32 )D16 - 32
19X-RAY DIFFRACTION19chain 'D' and (resid 33 through 123 )D33 - 123
20X-RAY DIFFRACTION20chain 'D' and (resid 124 through 198 )D124 - 198
21X-RAY DIFFRACTION21chain 'D' and (resid 199 through 261 )D199 - 261

+
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