1XQZ

Crystal Structure of hPim-1 kinase at 2.1 A resolution

Summary for 1XQZ

• Entry DOI: 10.2210/pdb1xqz/pdb
• Related: 1xr1
• Descriptor: Proto-oncogene serine/threonine-protein kinase Pim-1 (2 entities in total)
• Functional Keywords: protein kinase fold, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• Total number of polymer chains: 1
• Total formula weight: 34251.91

Authors

Qian, K.C.,Wang, L.,Hickey, E.R.,Studts, J.,Barringer, K.,Peng, C.,Kronkaitis, A.,Li, J.,White, A.,Mische, S.,Farmer, B. (deposition date: 2004-10-13, release date: 2004-11-09, Last modification date: 2024-02-14)

Primary citation

Qian, K.C.,Wang, L.,Hickey, E.R.,Studts, J.,Barringer, K.,Peng, C.,Kronkaitis, A.,Li, J.,White, A.,Mische, S.,Farmer, B.
Structural Basis of Constitutive Activity and a Unique Nucleotide Binding Mode of Human Pim-1 Kinase.
J.Biol.Chem., 280:6130-6137, 2005

PubMed Abstract: Pim-1 kinase is a member of a distinct class of serine/threonine kinases consisting of Pim-1, Pim-2, and Pim-3. Pim kinases are highly homologous to one another and share a unique consensus hinge region sequence, ER-PXPX, with its two proline residues separated by a non-conserved residue, but they (Pim kinases) have <30% sequence identity with other kinases. Pim-1 has been implicated in both cytokine-induced signal transduction and the development of lymphoid malignancies. We have determined the crystal structures of apo Pim-1 kinase and its AMP-PNP (5'-adenylyl-beta,gamma-imidodiphosphate) complex to 2.1-angstroms resolutions. The structures reveal the following. 1) The kinase adopts a constitutively active conformation, and extensive hydrophobic and hydrogen bond interactions between the activation loop and the catalytic loop might be the structural basis for maintaining such a conformation. 2) The hinge region has a novel architecture and hydrogen-bonding pattern, which not only expand the ATP pocket but also serve to establish unambiguously the alignment of the Pim-1 hinge region with that of other kinases. 3) The binding mode of AMP-PNP to Pim-1 kinase is unique and does not involve a critical hinge region hydrogen bond interaction. Analysis of the reported Pim-1 kinase-domain structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo.

PubMed: 15525646
DOI: 10.1074/jbc.M409123200

Experimental method

X-RAY DIFFRACTION (2.1 Å)