[English] 日本語
Yorodumi
- PDB-7nbm: Co-crystal structure of Human Nicotinamide N-methyltransferase (N... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7nbm
TitleCo-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with the bisubstrate-like inhibitor (33)
ComponentsNicotinamide N-methyltransferase
KeywordsTRANSFERASE / Methyl Transferase / drug discovery / Inhibitor complex / Nicotinamide / metabolic disorders
Function / homology
Function and homology information


pyridine N-methyltransferase activity / nicotinamide N-methyltransferase / nicotinamide N-methyltransferase activity / nicotinamide metabolic process / positive regulation of protein deacetylation / Metabolism of ingested SeMet, Sec, MeSec into H2Se / Methylation / : / positive regulation of gluconeogenesis / methylation / 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. / S-adenosyl-L-methionine-dependent methyltransferase superfamily
Similarity search - Domain/homology
Chem-U7K / Nicotinamide N-methyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.691 Å
AuthorsSchreuder, H.A. / Liesum, A.
CitationJournal: Molecules / Year: 2021
Title: Novel Inhibitors of Nicotinamide- N -Methyltransferase for the Treatment of Metabolic Disorders.
Authors: Kannt, A. / Rajagopal, S. / Hallur, M.S. / Swamy, I. / Kristam, R. / Dhakshinamoorthy, S. / Czech, J. / Zech, G. / Schreuder, H. / Ruf, S.
History
DepositionJan 27, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 17, 2021Provider: repository / Type: Initial release
Revision 1.1Jan 31, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)127,8158
Polymers125,8644
Non-polymers1,9504
Water4,774265
1
A: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9542
Polymers31,4661
Non-polymers4881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9542
Polymers31,4661
Non-polymers4881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9542
Polymers31,4661
Non-polymers4881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Nicotinamide N-methyltransferase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,9542
Polymers31,4661
Non-polymers4881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)45.301, 61.973, 108.197
Angle α, β, γ (deg.)92.48, 98.14, 111.43
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 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): DE
References: UniProt: P40261, nicotinamide N-methyltransferase
#2: Chemical
ChemComp-U7K / (E)-3-((5,6-dihydro-2H,4H-thiazolo[5,4,3-ij]quinolin-2-ylidene)amino)-2-hydroxy-1-(4-(isoquinolin-5-yl)piperazin-1-yl)-2-methylpropan-1-one / (2~{S})-1-(4-isoquinolin-5-ylpiperazin-1-yl)-2-methyl-2-oxidanyl-3-[(~{E})-3-thia-1-azatricyclo[6.3.1.0^{4,12}]dodeca-4(12),5,7-trien-2-ylideneamino]propan-1-one


Mass: 487.616 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C27H29N5O2S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 265 / 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: 2.21 Å3/Da / Density % sol: 44.4 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: Human NNMT was crystallized using the following conditions: A protein solution with 6 mg/ml NNMT, 50 mM Tris/HCL, pH 8.0, 1 mM DTT, 0.95mM inhibitor and 5% v/v glycerol was equilibrated at ...Details: Human NNMT was crystallized using the following conditions: A protein solution with 6 mg/ml NNMT, 50 mM Tris/HCL, pH 8.0, 1 mM DTT, 0.95mM inhibitor and 5% v/v glycerol was equilibrated at room temperature in a hanging drop setup against 2.2 M ammonium sulfate with 0.1 M HEPES/Na, pH 7.6. Small crystal appeared after 1-2 weeks.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.99999 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Dec 6, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99999 Å / Relative weight: 1
ReflectionResolution: 2.69→41.97 Å / Num. obs: 26311 / % possible obs: 88 % / Redundancy: 1.7 % / CC1/2: 0.991 / Rmerge(I) obs: 0.077 / Rrim(I) all: 0.109 / Net I/σ(I): 7.2
Reflection shellResolution: 2.69→2.85 Å / Redundancy: 1.5 % / Rmerge(I) obs: 0.483 / Mean I/σ(I) obs: 1.7 / Num. unique obs: 3895 / CC1/2: 0.651 / Rrim(I) all: 0.684 / % possible all: 81.2

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (6-FEB-2020)refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7BKG

7bkg


Resolution: 2.691→41.97 Å / Cor.coef. Fo:Fc: 0.917 / Cor.coef. Fo:Fc free: 0.804 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 0.484
RfactorNum. reflection% reflectionSelection details
Rfree0.3144 1317 -RANDOM
Rwork0.2088 ---
obs0.2141 26310 88 %-
Displacement parametersBiso mean: 48 Å2
Baniso -1Baniso -2Baniso -3
1--4.8617 Å2-3.5181 Å2-0.1083 Å2
2--5.2033 Å20.1549 Å2
3----0.3416 Å2
Refine analyzeLuzzati coordinate error obs: 0.37 Å
Refinement stepCycle: LAST / Resolution: 2.691→41.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8104 0 140 265 8509
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0088437HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.0611444HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2918SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes1380HARMONIC5
X-RAY DIFFRACTIONt_it8437HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion1060SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact6943SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.12
X-RAY DIFFRACTIONt_other_torsion21.85
LS refinement shellResolution: 2.691→2.72 Å
RfactorNum. reflection% reflection
Rfree0.3247 17 -
Rwork0.2816 --
obs--53.16 %

+
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