1IAN

HUMAN P38 MAP KINASE INHIBITOR COMPLEX

Summary for 1IAN

• Entry DOI: 10.2210/pdb1ian/pdb
• Descriptor: P38 MAP KINASE, 4-[5-(3-IODO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-1H-IMIDAZOL-4-YL]-PYRIDINE (2 entities in total)
• Functional Keywords: protein ser/thr-kinase, serine/threonine-protein kinase, serine-threonine-protein kinase complex
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q16539
• Total number of polymer chains: 1
• Total formula weight: 43561.03

Authors

Tong, L. (deposition date: 1997-03-07, release date: 1998-05-06, Last modification date: 2024-04-03)

Primary citation

Tong, L.,Pav, S.,White, D.M.,Rogers, S.,Crane, K.M.,Cywin, C.L.,Brown, M.L.,Pargellis, C.A.
A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket.
Nat.Struct.Biol., 4:311-316, 1997

PubMed Abstract: The crystal structure of human p38 mitogen-activated protein (MAP) kinase in complex with a potent and highly specific pyridinyl-imidazole inhibitor has been determined at 2.0 A resolution. The structure of the kinase, which is in its unphosphorylated state, is similar to that of the closely-related ERK2. The inhibitor molecule is bound in the ATP pocket. A hydrogen bond is made between the pyridyl nitrogen of the inhibitor and the main chain amido nitrogen of residue 109, analogous to the interaction from the N1 atom of ATP. The crystal structure provides possible explanations for the specificity of this class of inhibitors. Other protein kinase inhibitors may achieve their specificity through a similar mechanism. The structure also reveals a possible second binding site for this inhibitor, with currently unknown function.

PubMed: 9095200
DOI: 10.1038/nsb0497-311

Experimental method

X-RAY DIFFRACTION (2 Å)