5LGQ

Crystal structure of mouse CARM1 in complex with ligand P2C3s


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Transition state mimics are valuable mechanistic probes for structural studies with the arginine methyltransferase CARM1.

van Haren, M.J.Marechal, N.Troffer-Charlier, N.Cianciulli, A.Sbardella, G.Cavarelli, J.Martin, N.I.

(2017) Proc Natl Acad Sci U S A 114: 3625-3630

  • DOI: https://doi.org/10.1073/pnas.1618401114
  • Primary Citation of Related Structures:  
    5LGP, 5LGQ, 5LGR, 5LGS

  • PubMed Abstract: 

    Coactivator associated arginine methyltransferase 1 (CARM1) is a member of the protein arginine methyltransferase (PRMT) family and methylates a range of proteins in eukaryotic cells. Overexpression of CARM1 is implicated in a number of cancers, and it is therefore seen as a potential therapeutic target. Peptide sequences derived from the well-defined CARM1 substrate poly(A)-binding protein 1 (PABP1) were covalently linked to an adenosine moiety as in the AdoMet cofactor to generate transition state mimics. These constructs were found to be potent CARM1 inhibitors and also formed stable complexes with the enzyme. High-resolution crystal structures of CARM1 in complex with these compounds confirm a mode of binding that is indeed reflective of the transition state at the CARM1 active site. Given the transient nature of PRMT-substrate complexes, such transition state mimics represent valuable chemical tools for structural studies aimed at deciphering the regulation of arginine methylation mediated by the family of arginine methyltransferases.


  • Organizational Affiliation

    Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-arginine methyltransferase CARM1
A, B, C, D
361Mus musculusMutation(s): 0 
Gene Names: Carm1Prmt4
EC: 2.1.1.319
UniProt & NIH Common Fund Data Resources
Find proteins for Q9WVG6 (Mus musculus)
Explore Q9WVG6 
Go to UniProtKB:  Q9WVG6
IMPC:  MGI:1913208
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WVG6
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Polyadenylate-binding protein 1E [auth F],
F [auth E],
G,
H
11Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P11940 (Homo sapiens)
Explore P11940 
Go to UniProtKB:  P11940
PHAROS:  P11940
GTEx:  ENSG00000070756 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11940
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8ZB
Query on 8ZB

Download Ideal Coordinates CCD File 
W [auth F],
X [auth E],
Y [auth G],
Z [auth H]
(2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-propyl-oxolane-3,4-diol
C12 H17 N5 O3
BKDAOQOLDUJANJ-WOUKDFQISA-N
PG6
Query on PG6

Download Ideal Coordinates CCD File 
M [auth A]1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE
C12 H26 O6
DMDPGPKXQDIQQG-UHFFFAOYSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
J [auth A],
K [auth A],
T [auth C],
V [auth D]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
N [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
DXE
Query on DXE

Download Ideal Coordinates CCD File 
L [auth A]1,2-DIMETHOXYETHANE
C4 H10 O2
XTHFKEDIFFGKHM-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
I [auth A]
O [auth B]
P [auth B]
Q [auth B]
R [auth C]
I [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth C],
S [auth C],
U [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.706α = 90
b = 99.011β = 90
c = 207.306γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-03-22
    Type: Initial release
  • Version 1.1: 2017-04-05
    Changes: Non-polymer description
  • Version 1.2: 2017-04-12
    Changes: Database references
  • Version 2.0: 2024-01-10
    Changes: Atomic model, Data collection, Database references, Refinement description