PDBsum entry 6tca

Signaling protein

PDB id: 6tca

Contents

Protein chains

345 a.a.

346 a.a.

326 a.a.

Ligands

39G ×4

PDB id:

6tca

Name:

Signaling protein

Title:

Phosphorylated p38 and mapkapk2 complex with inhibitor

Structure:

Map kinase-activated protein kinase 2. Chain: a, c, e, g. Synonym: mk2. Engineered: yes. Mitogen-activated protein kinase 14. Chain: b, d, f, h. Synonym: mapk 14,cytokine suppressive anti-inflammatory drug-binding protein,csbp,map kinase mxi2,max-interacting protein 2,mitogen- activated protein kinase p38 alpha,map kinase p38 alpha,stress-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mapkapk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2, sapk2a. Expression_system_taxid: 562

Resolution:

3.70Å R-factor: 0.254 R-free: 0.297

Authors:

P.Sok,A.Remenyi

Key ref:

P.Sok et al. (2020). MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases. Structure, 28, 1101. PubMed id: 32649858 DOI: 10.1016/j.str.2020.06.007

Date:

05-Nov-19 Release date: 22-Jul-20

Protein chain

P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens

Seq: 400 a.a.

Struc: 345 a.a.

Protein chains

Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14 from Homo sapiens

Seq: 360 a.a.

Struc: 346 a.a.*

Protein chains

P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens

Seq: 400 a.a.

Struc: 326 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, C, E, G: 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⁺
• Enzyme class 2: Chains B, D, F, H: E.C.2.7.11.24 - mitogen-activated 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⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.str.2020.06.007

Structure 28:1101 (2020)

PubMed id: 32649858

MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.

P.Sok, G.Gógl, G.S.Kumar, A.Alexa, N.Singh, K.Kirsch, A.Sebő, L.Drahos, Z.Gáspári, W.Peti, A.Reményi.

ABSTRACT

Mitogen-activated protein kinases (MAPKs) control essential eukaryotic signaling pathways. While much has been learned about MAPK activation, much less is known about substrate recruitment and specificity. MAPK substrates may be other kinases that are crucial to promote a further diversification of the signaling outcomes. Here, we used a variety of molecular and cellular tools to investigate the recruitment of two substrate kinases, RSK1 and MK2, to three MAPKs (ERK2, p38α, and ERK5). Unexpectedly, we identified that kinase heterodimers form structurally and functionally distinct complexes depending on the activation state of the MAPK. These may be incompatible with downstream signaling, but naturally they may also form structures that are compatible with the phosphorylation of the downstream kinase at the activation loop, or alternatively at other allosteric sites. Furthermore, we show that small-molecule inhibitors may affect the quaternary arrangement of kinase heterodimers and thus influence downstream signaling in a specific manner.