Modelling and molecular dynamics of the interaction between the E3 ubiquitin ligase Itch and the E2 UbcH7.

@article{Raimondo2008ModellingAM,
  title={Modelling and molecular dynamics of the interaction between the E3 ubiquitin ligase Itch and the E2 UbcH7.},
  author={Domenico Raimondo and Alejandro Giorgetti and Francesca Bernassola and Gerry Melino and Anna Tramontano},
  journal={Biochemical pharmacology},
  year={2008},
  volume={76 11},
  pages={
          1620-7
        }
}

Figures and Tables from this paper

Loop 7 of E2 Enzymes: An Ancestral Conserved Functional Motif Involved in the E2-Mediated Steps of the Ubiquitination Cascade
TLDR
It is shown that acidic loop is a conserved ancestral motif in E2s, relying on the presence of alternate hydrophobic and acidic residues, and suggest a crucial role for L7 of family 3 E 2s in all the E2-mediated steps of the ubiquitination cascade.
The E2 Ubiquitin-conjugating Enzymes Direct Polyubiquitination to Preferred Lysines
TLDR
The data indicate that the E2 enzymes are capable of directing the ubiquitination process to distinct subsets of ubiquitin lysines, depending on the specific E2 utilized, and support the rising notion that the functional unit of E2 is a dimer.
HECT-Type E3 Ubiquitin Ligases in Cancer.
Ubiquitin: molecular modeling and simulations.
Airway Inflammation via UbcH7 Ndfip1 Regulates Itch Ligase Activity and
TLDR
It is found that nontypeable Haemophilus influenzae induces the association of Itch with Ndfip1, and these results provide new mechanistic insights into how Itch function is regulated during in flammatory signaling, which could be exploited therapeutically in in-in-ammatory diseases.
High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy
TLDR
ITCH inhibitors reduce cancer cell growth, and synergize with gemcitabine or mitomycin in killing cancer cells by blocking autophagy, and insight is provided into how clomipramine and its structural homologs might interfere with ITCH and other HECT E3 ligase catalytic activity in potentiating chemotherapy by regulating autophagic fluxes.
Ndfip1 Regulates Itch Ligase Activity and Airway Inflammation via UbcH7
TLDR
It is found that nontypeable Haemophilus influenzae induces the association of Itch with Ndfip1, which provides new mechanistic insights into how Itch function is regulated during inflammatory signaling, which could be exploited therapeutically in inflammatory diseases.
Atomistic Insights Into the Regulatory Mechanisms Mediated by Post- Translational Modifications: Molecular Dynamics Investigations
TLDR
This contribution reviews several recent studies devoted to molecular dynamics simulations of phospho-proteins with particular attention to proteins involved in the p53 pathway, ubiquitin pathway, protein kinases and intrinsically disordered proteins.
Role of Rsp5 ubiquitin ligase in biogenesis of rRNA, mRNA and tRNA in yeast
TLDR
A comprehensive review of the nuclear and cytoplasmic functions of Rsp5 with a focus on biogenesis of different RNAs and the involvement of RSP5 in controlling diverse cellular mechanisms at multiple levels and in adaptation of the cell to changing growth conditions is highlighted.
Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch
TLDR
The role of this HECT E3 ubiquitin ligase Itch in suppressing Hh-dependent tumours is reviewed and its potential as promising target for innovative therapeutic approaches is explored.
...
...

References

SHOWING 1-10 OF 41 REFERENCES
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.
Characterization of Human hect Domain Family Members and Their Interaction with UbcH5 and UbcH7*
TLDR
It is shown that the hect domain of E6-AP is necessary and sufficient for ubiquitin thioester adduct formation, and in further support of the hypothesis that hect domain proteins represent a family of E3s, several of these are shown to formThioester complexes with UbcH7.
Autoinhibition of the HECT-Type Ubiquitin Ligase Smurf2 through Its C2 Domain
The Tail of a Ubiquitin-conjugating Enzyme Redirects Multi-ubiquitin Chain Synthesis from the Lysine 48-linked Configuration to a Novel Nonlysine-linked Form*
TLDR
The UBC1 enzyme assembles onto itself a multi-ubiquitin chain in vitro whose linkage configuration is dependent on the unconserved carboxyl-terminal extension or tail that is appended to its catalytic domain, thereby supporting the emerging view that Ub can be attached to itself or other proteins in a variety of ways.
Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change.
TLDR
This work has identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222, which are located within a Pro-rich region and induces a conformational change that greatly enhances the catalytic activity of Itch, a HECT E3 ligase found to be directly activated upon itsosphorylation.
The E3 ubiquitin ligase Itch controls the protein stability of p63
TLDR
It is shown that the Hect (homologous to the E6-associated protein C terminus)-containing Nedd4-like ubiquitin protein ligase Itch binds, ubiquitylates, and promotes the degradation of p63, suggesting that Itch has a fundamental role in the mechanism that controls endogenous p63 protein levels and therefore contributes to regulation of p 63 in physiological conditions.
Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase
TLDR
The crystal structure of SopA in two conformations suggests that SopA is a unique HECT E3 ligase evolved from the coevolutionary selective pressure at the bacterium-host interface.
The ubiquitin–protein ligase Itch regulates p73 stability
TLDR
This work has identified a key mechanism in the control of p73 protein levels both in normal as well as in stress conditions, and selectively binds and ubiquitinates p73 but not p53, which results in the rapid proteasome‐dependent degradation of p 73.
...
...