ISDA: 3KC3

Deposition Date 2009-10-20

Release Date 2010-01-12

Last Version Date 2024-02-21

Entry Detail

PDB ID:

3KC3

Keywords:

TRANSFERASE

Title:

MK2 complexed to inhibitor N4-(7-(benzofuran-2-yl)-1H-indazol-5-yl)pyrimidine-2,4-diamine

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.90 Å

R-Value Free:

0.29

R-Value Work:

0.22

R-Value Observed:

0.23

Space Group:

P 21 21 21

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:MAP kinase-activated protein
Gene (Uniprot):MAPKAPK2
Chain IDs:A, B, C, D, E, F, G, H, I, J, K, L
Chain Length:324
Number of Molecules:12
Biological Source:Homo sapiens

UniProt ID:P49137 Pfam ID:PF00069 EC:2.7.11.1

Ligand Molecules

MK2

Primary Citation

2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode.

Argiriadi, M.A, Ericsson, A.M, Harris, C.M, Banach, D.L, Borhani, D.W, Calderwood, D.J, Demers, M.D, Dimauro, J, Dixon, R.W, Hardman, J, Kwak, S, Li, B, Mankovich, J.A, Marcotte, D, Mullen, K.D, Ni, B, Pietras, M, Sadhukhan, R, Sousa, S, Tomlinson, M.J, Wang, L, Xiang, T, Talanian, R.V.Show

Bioorg. Med. Chem. Lett. 20 330 333 (2010)

PMID: 19919896 DOI: 10.1016/j.bmcl.2009.10.102

Abstact

MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter.

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Primary Citation of related structures

Abstact

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