3UIB

Map kinase LMAMPK10 from leishmania major in complex with SB203580


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The Crystal Structure of the MAP Kinase LmaMPK10 from Leishmania Major Reveals Parasite-Specific Features and Regulatory Mechanisms.

Horjales, S.Schmidt-Arras, D.Limardo, R.R.Leclercq, O.Obal, G.Prina, E.Turjanski, A.G.Spath, G.F.Buschiazzo, A.

(2012) Structure 20: 1649-1660

  • DOI: https://doi.org/10.1016/j.str.2012.07.005
  • Primary Citation of Related Structures:  
    3PG1, 3UIB

  • PubMed Abstract: 

    Mitogen-activated protein kinases (MAPKs) are involved in environmental signal sensing. They are thus expected to play key roles in the biology of Trypanosomatid parasites, which display complex life cycles and use extracellular cues to modulate cell differentiation. Despite their relevance, structural data of Trypanosomatid MAPKs is lacking. We have now determined the crystal structure of Leishmania major LmaMPK10, a stage-specifically activated MAPK, both alone and in complex with SB203580. LmaMPK10 was observed to be more similar to p38 than to other human MAPKs. However, significant differences could be identified in the catalytic pocket, as well as in potentially regulatory sites in the N-terminal lobe. The modified pocket architecture in LmaMPK10 precludes DFG-in/DFG-out regulatory flipping as observed in mammalian MAPKs. LmaMPK10-nucleotide association was also studied, revealing a potential C-terminal autoinhibitory mechanism. Overall, these data should speed the discovery of molecules interfering with LmaMPK10 functions, with relevance for antileishmanial drug development strategies.


  • Organizational Affiliation

    Unit of Protein Crystallography, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
mitogen-activated protein kinase362Leishmania majorMutation(s): 0 
Gene Names: LMJF10.0200LMJF_10_0200
EC: 2.7.11.1
UniProt
Find proteins for Q4QHJ8 (Leishmania major)
Explore Q4QHJ8 
Go to UniProtKB:  Q4QHJ8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ4QHJ8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SB2
Query on SB2

Download Ideal Coordinates CCD File 
B [auth A]4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE
C21 H16 F N3 O S
CDMGBJANTYXAIV-MHZLTWQESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SB2 PDBBind:  3UIB Kd: 160 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.9α = 90
b = 80.9β = 90
c = 131.02γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
AMoREphasing
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
MOSFLMdata reduction
BUSTERrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-19
    Type: Initial release
  • Version 1.1: 2012-10-31
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations