1phk
From Proteopedia
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TWO STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHORYLASE, KINASE: AN ACTIVE PROTEIN KINASE COMPLEXED WITH NUCLEOTIDE, SUBSTRATE-ANALOGUE AND PRODUCT
Overview
BACKGROUND: Control of intracellular events by protein phosphorylation is, promoted by specific protein kinases. All the known protein kinase possess, a common structure that defines a catalytically competent entity termed, the 'kinase catalytic core'. Within this common structural framework each, kinase displays its own unique substrate specificity, and a regulatory, mechanism that may be modulated by association with other proteins., Structural studies of phosphorylase kinase (Phk), the major substrate of, which is glycogen phosphorylase, may be expected to shed light on its, regulation. RESULTS: We report two crystal structures of the catalytic, core (residues 1-298; Phk gamma trnc) of the gamma-subunit of rabbit, muscle phosphorylase kinase: the binary complex with, Mn2+/beta-gamma-imidoadenosine 5'-triphosphate (AMPPNP) to a resolution of, 2.6 A and the binary complex with Mg2+/ADP to a resolution of 3.0 A. The, structures were solved by molecular replacement using the cAMP-dependent, protein kinase (cAPK) as a model. CONCLUSIONS: The overall structure of, Phk gamma trnc is similar to that of the catalytic core of other protein, kinases. It consists of two domians joined on one edge by a 'hinge', with, the catalytic site located in the cleft between the domains. Phk gamma, trnc is constitutively active, and lacks the need for an activatory, phosphorylation event that is essential for many kinases. The structure, exhibits an essentially 'closed' conformation of the domains which is, similar to that of cAPK complexed with substrates. The phosphorylated, residue that is located at the domain interface in many protein kinases, and that is believed to stabilize an active conformation is substituted by, a glutamate in Phk gamma trnc. The glutamate, in a similar manner to the, phosphorylated residue in other protein kinases, interacts with an, arginine adjacent to the catalytic aspartate but does not participate in, interdomain contacts. The interactions between the enzyme and the, nucleotide product of its activity, Mg2+/ADP, explain the inhibitory, properties of the nucleotides that are observed in kinetic studies.
About this Structure
1PHK is a Single protein structure of sequence from Oryctolagus cuniculus with MN and ATP as ligands. Active as Phosphorylase kinase, with EC number 2.7.11.19 Full crystallographic information is available from OCA.
Reference
Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product., Owen DJ, Noble ME, Garman EF, Papageorgiou AC, Johnson LN, Structure. 1995 May 15;3(5):467-82. PMID:7663944
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