1xr1
From Proteopedia
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Crystal structure of hPim-1 kinase in complex with AMP-PNP at 2.1 A Resolution
Overview
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.
About this Structure
1XR1 is a Single protein structure of sequence from Homo sapiens with MG and ANP as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase., Qian KC, Wang L, Hickey ER, Studts J, Barringer K, Peng C, Kronkaitis A, Li J, White A, Mische S, Farmer B, J Biol Chem. 2005 Feb 18;280(7):6130-7. Epub 2004 Nov 3. PMID:15525646
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