PDBsum entry 3uib

Transferase

PDB id: 3uib

Contents

Protein chain

309 a.a.

Ligands

SB2

Waters ×59

PDB id:

3uib

Name:

Transferase

Title:

Map kinase lmampk10 from leishmania major in complex with sb203580

Structure:

Mitogen-activated protein kinase. Chain: a. Engineered: yes

Source:

Leishmania major. Organism_taxid: 5664. Gene: lmjf10.0200, lmjf_10_0200. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.65Å R-factor: 0.217 R-free: 0.241

Authors:

S.Horjales,D.Schmidt-Arras,O.Leclercq,G.Spath,A.Buschiazzo

Key ref:

S.Horjales et al. (2012). The crystal structure of the MAP kinase LmaMPK10 from Leishmania major reveals parasite-specific features and regulatory mechanisms. Structure, 20, 1649-1660. PubMed id: 22884419

Date:

04-Nov-11 Release date: 19-Sep-12

Protein chain

Q4QHJ8  (Q4QHJ8_LEIMA) -  Putative mitogen-activated protein kinase from Leishmania major

Seq: 407 a.a.

Struc: 309 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Structure 20:1649-1660 (2012)

PubMed id: 22884419

The crystal structure of the MAP kinase LmaMPK10 from Leishmania major reveals parasite-specific features and regulatory mechanisms.

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

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.