1U4D

Structure of the ACK1 Kinase Domain bound to Debromohymenialdisine

Summary for 1U4D

• Entry DOI: 10.2210/pdb1u4d/pdb
• Related: 1U46 1U54
• Descriptor: Activated CDC42 kinase 1, DEBROMOHYMENIALDISINE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: tyrosine kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: Q07912
• Total number of polymer chains: 2
• Total formula weight: 66642.02

Authors

Lougheed, J.C.,Chen, R.H.,Mak, P.,Stout, T.J. (deposition date: 2004-07-23, release date: 2004-08-31, Last modification date: 2023-08-23)

Primary citation

Lougheed, J.C.,Chen, R.H.,Mak, P.,Stout, T.J.
Crystal Structures of the Phosphorylated and Unphosphorylated Kinase Domains of the Cdc42-associated Tyrosine Kinase ACK1.
J.Biol.Chem., 279:44039-44045, 2004

PubMed Abstract: ACK1 is a multidomain non-receptor tyrosine kinase that is an effector of the Cdc42 GTPase. Members of the ACK family have a unique domain ordering and are the only tyrosine kinases known to interact with Cdc42. In contrast with many protein kinases, ACK1 has only a modest increase in activity upon phosphorylation. We have solved the crystal structures of the human ACK1 kinase domain in both the unphosphorylated and phosphorylated states. Comparison of these structures reveals that ACK1 adopts an activated conformation independent of phosphorylation. Furthermore, the unphosphorylated activation loop is structured, and its conformation resembles that seen in activated tyrosine kinases. In addition to the apo structure, complexes are also presented with a non-hydrolyzable nucleotide analog (adenosine 5'-(beta,gamma-methylenetriphosphate)) and with the natural product debromohymenialdisine, a general inhibitor of many protein kinases. Analysis of these structures reveals a typical kinase fold, a pre-organization into the activated conformation, and an unusual substrate-binding cleft.

PubMed: 15308621
DOI: 10.1074/jbc.M406703200

Experimental method

X-RAY DIFFRACTION (2.1 Å)