1smh

Protein kinase A variant complex with completely ordered N-terminal helixProtein kinase A variant complex with completely ordered N-terminal helix

Structural highlights 1smh is a 2 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.044Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAPCA_BOVIN Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Protein kinases comprise the major enzyme family critically involved in signal transduction pathways; posttranslational modifications affect their regulation and determine signaling states. The prototype protein kinase A (PKA) possesses an N-terminal alpha-helix (Helix A) that is atypical for kinases and is thus a major distinguishing feature of PKA. Its physiological function may involve myristoylation at the N-terminus and modulation via phosphorylation at serine 10. Here we describe an unusual structure of an unmyristoylated PKA, unphosphorylated at serine 10, with a completely ordered N-terminus. Using standard conditions (e.g., PKI 5-24, ATP site ligand, MEGA-8), a novel 2-fold phosphorylated PKA variant showed the ordered N-terminus in a new crystal packing arrangement. Thus, the critical factor for structuring the N-terminus is apparently the absence of phosphorylation of Ser10. The flexibility of the N-terminus, its myristoylation, and the conformational dependence on the phosphorylation state are consistent with a functional role for myristoylation. The typically disordered N-terminus of PKA can fold as a helix and project the myristoylation site into solution.,Breitenlechner C, Engh RA, Huber R, Kinzel V, Bossemeyer D, Gassel M Biochemistry. 2004 Jun 22;43(24):7743-9. PMID:15196017 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CAMP-dependent protein kinase 3D structures

spinqualitylabelsall models 1smh, resolution 2.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image