5ES1

CRYSTAL STRUCTURE OF MICROTUBULE AFFINITY-REGULATING KINASE 4 CATALYTIC DOMAIN IN COMPLEX WITH A PYRAZOLOPYRIMIDINE INHIBITOR

Summary for 5ES1

• Entry DOI: 10.2210/pdb5es1/pdb
• Descriptor: MAP/microtubule affinity-regulating kinase 4, ~{N}-[(1~{R},6~{R})-6-azanyl-2,2-bis(fluoranyl)cyclohexyl]-5-ethyl-4-[6-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide (3 entities in total)
• Functional Keywords: mark4 par-1 serine/threonine protein kinase11, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q96L34
• Total number of polymer chains: 1
• Total formula weight: 38092.83

Authors

Sack, J.S. (deposition date: 2015-11-16, release date: 2015-12-02, Last modification date: 2023-09-27)

Primary citation

Sack, J.S.,Gao, M.,Kiefer, S.E.,Myers, J.E.,Newitt, J.A.,Wu, S.,Yan, C.
Crystal structure of microtubule affinity-regulating kinase 4 catalytic domain in complex with a pyrazolopyrimidine inhibitor.
Acta Crystallogr F Struct Biol Commun, 72:129-134, 2016

PubMed Abstract: Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine kinase involved in the phosphorylation of MAP proteins that regulate microtubule dynamics. Abnormal activity of MARK4 has been proposed to contribute to neurofibrillary tangle formation in Alzheimer's disease. The crystal structure of the catalytic and ubiquitin-associated domains of MARK4 with a potent pyrazolopyrimidine inhibitor has been determined to 2.8 Å resolution with an Rwork of 22.8%. The overall structure of MARK4 is similar to those of the other known MARK isoforms. The inhibitor is located in the ATP-binding site, with the pyrazolopyrimidine group interacting with the inter-lobe hinge region while the aminocyclohexane moiety interacts with the catalytic loop and the DFG motif, forcing the activation loop out of the ATP-binding pocket.

PubMed: 26841763
DOI: 10.1107/S2053230X15024747

Experimental method

X-RAY DIFFRACTION (2.8 Å)