5E1D

NTMT1 in complex with YPKRIA peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.169 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.154 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis for substrate recognition by the human N-terminal methyltransferase 1.

Dong, C.Mao, Y.Tempel, W.Qin, S.Li, L.Loppnau, P.Huang, R.Min, J.

(2015) Genes Dev 29: 2343-2348

  • DOI: https://doi.org/10.1101/gad.270611.115
  • Primary Citation of Related Structures:  
    5E1B, 5E1D, 5E1M, 5E1O, 5E2A, 5E2B

  • PubMed Abstract: 

    α-N-terminal methylation represents a highly conserved and prevalent post-translational modification, yet its biological function has remained largely speculative. The recent discovery of α-N-terminal methyltransferase 1 (NTMT1) and its physiological substrates propels the elucidation of a general role of α-N-terminal methylation in mediating DNA-binding ability of the modified proteins. The phenotypes, observed from both NTMT1 knockdown in breast cancer cell lines and knockout mouse models, suggest the potential involvement of α-N-terminal methylation in DNA damage response and cancer development. In this study, we report the first crystal structures of human NTMT1 in complex with cofactor S-adenosyl-L-homocysteine (SAH) and six substrate peptides, respectively, and reveal that NTMT1 contains two characteristic structural elements (a β hairpin and an N-terminal extension) that contribute to its substrate specificity. Our complex structures, coupled with mutagenesis, binding, and enzymatic studies, also present the key elements involved in locking the consensus substrate motif XPK (X indicates any residue type other than D/E) into the catalytic pocket for α-N-terminal methylation and explain why NTMT1 prefers an XPK sequence motif. We propose a catalytic mechanism for α-N-terminal methylation. Overall, this study gives us the first glimpse of the molecular mechanism of α-N-terminal methylation and potentially contributes to the advent of therapeutic agents for human diseases associated with deregulated α-N-terminal methylation.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Toronto, Toronto, Ontaria M5G 1L7, Canada;


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
N-terminal Xaa-Pro-Lys N-methyltransferase 1
A, B
241Homo sapiensMutation(s): 0 
Gene Names: NTMT1C9orf32METTL11ANRMTNRMT1AD-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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
RCC1C [auth D],
D [auth E]
6Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P18754 (Homo sapiens)
Explore P18754 
Go to UniProtKB:  P18754
PHAROS:  P18754
GTEx:  ENSG00000180198 
Entity Groups  
UniProt GroupP18754
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH

Download Ideal Coordinates CCD File 
E [auth A],
TA [auth B]
S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
H [auth A],
UA [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
UNX
Query on UNX

Download Ideal Coordinates CCD File 
AA [auth A]
AB [auth B]
BA [auth A]
BB [auth B]
CA [auth A]
AA [auth A],
AB [auth B],
BA [auth A],
BB [auth B],
CA [auth A],
CB [auth B],
DA [auth A],
DB [auth B],
EA [auth A],
EB [auth B],
FA [auth A],
FB [auth B],
GA [auth A],
GB [auth B],
HA [auth A],
HB [auth B],
I [auth A],
IA [auth A],
IB [auth B],
J [auth A],
JA [auth A],
JB [auth B],
K [auth A],
KA [auth A],
KB [auth B],
L [auth A],
LA [auth A],
LB [auth B],
M [auth A],
MA [auth A],
MB [auth B],
N [auth A],
NA [auth A],
NB [auth B],
O [auth A],
OA [auth A],
OB [auth B],
P [auth A],
PA [auth A],
Q [auth A],
QA [auth A],
R [auth A],
RA [auth A],
S [auth A],
SA [auth A],
T [auth A],
U [auth A],
V [auth A],
VA [auth B],
W [auth A],
WA [auth B],
X [auth A],
XA [auth B],
Y [auth A],
YA [auth B],
Z [auth A],
ZA [auth B]
UNKNOWN ATOM OR ION
X
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.45 Å
  • R-Value Free: 0.169 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.154 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.082α = 90
b = 107.082β = 90
c = 205.946γ = 120
Software Package:
Software NamePurpose
Aimlessdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-10-28
    Type: Initial release
  • Version 1.1: 2015-11-18
    Changes: Database references
  • Version 1.2: 2015-12-02
    Changes: Database references
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references, Derived calculations