4q5h

Shigella Effector Kinase OspG bound to AMPPNP and E2-Ub UbcH7-Ub ConjugateShigella Effector Kinase OspG bound to AMPPNP and E2-Ub UbcH7-Ub Conjugate

Structural highlights 4q5h is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 4qse Activity: Ubiquitin--protein ligase, with EC number 6.3.2.19 Resources: FirstGlance, OCA, RCSB, PDBsum Function [OSPG_SHISS] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is a kinase that is involved in down-regulation of the host innate response induced by invasive bacteria (By similarity). [UB2L3_HUMAN] Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PARK2 and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. [UBI4P_YEAST] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Publication Abstract from PubMed Shigella invasion of its human host is assisted by T3SS-delivered effector proteins. The OspG effector kinase binds ubiquitin and ubiquitin-loaded E2-conjugating enzymes, including UbcH5b and UbcH7, and attenuates the host innate immune NF-kB signaling. We present the structure of OspG bound to the UbcH7 approximately Ub conjugate. OspG has a minimal kinase fold lacking the activation loop of regulatory kinases. UbcH7 approximately Ub binds OspG at sites remote from the kinase active site, yet increases its kinase activity. The ubiquitin is positioned in the "open" conformation with respect to UbcH7 using its I44 patch to interact with the C terminus of OspG. UbcH7 binds to OspG using two conserved loops essential for E3 ligase recruitment. The interaction of the UbcH7 approximately Ub with OspG is remarkably similar to the interaction of an E2 approximately Ub with a HECT E3 ligase. OspG interferes with the interaction of UbcH7 with the E3 parkin and inhibits the activity of the E3. Structural Basis for the Inhibition of Host Protein Ubiquitination by Shigella Effector Kinase OspG.,Grishin AM, Condos TE, Barber KR, Campbell-Valois FX, Parsot C, Shaw GS, Cygler M Structure. 2014 Jun 10;22(6):878-88. doi: 10.1016/j.str.2014.04.010. Epub 2014, May 22. PMID:24856362 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4q5h, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image