6DTN

The structure of NTMT1 in complex with compound DC100-1

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.169 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1.

Chen, D., Dong, G., Noinaj, N., Huang, R.

(2019) J Med Chem 62: 3773-3779

  • DOI: https://doi.org/10.1021/acs.jmedchem.9b00206
  • Primary Citation of Related Structures:  
    6DTN

  • PubMed Abstract: 

    Protein N-terminal methyltransferase 1 (NTMT1) plays an important role in regulating mitosis and DNA repair. Here, we describe the discovery of a potent NTMT1 bisubstrate inhibitor 4 (IC 50 = 35 ± 2 nM) that exhibits greater than 100-fold selectivity against a panel of methyltransferases. We also report the first crystal structure of NTMT1 in complex with an inhibitor, which revealed that 4 occupies substrate and cofactor binding sites of NTMT1.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry and Molecular Pharmacology, Center for Cancer Research, Institute for Drug Discovery , Purdue University , West Lafayette , Indiana 47907 , United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
N-terminal Xaa-Pro-Lys N-methyltransferase 1A [auth B]241Homo sapiensMutation(s): 0 
Gene Names: NTMT1, C9orf32, METTL11A, NRMT, NRMT1, AD-003
EC: 2.1.1.244
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BV86 (Homo sapiens)
Explore Q9BV86 
Go to UniProtKB:  Q9BV86
PHAROS:  Q9BV86
GTEx:  ENSG00000148335 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BV86
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
(6D6)PPKRIA(NH2), DC100-1B [auth A]8synthetic constructMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.169 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.166α = 90
b = 73.166β = 90
c = 82.361γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United States1U01CA214649-01
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States1R01GM117275-01A1

Revision History  (Full details and data files)

  • Version 1.0: 2019-04-03
    Type: Initial release
  • Version 1.1: 2019-04-24
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.3: 2023-10-11
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description