Sandbox Reserved 1656: Difference between revisions
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==== Catalytic domain ==== | ==== Catalytic domain ==== | ||
The DUB family is determined by the catalytic domain. Indeed, DUBs belonging to the family of cysteine proteases have a catalytic site composed of two or three amino acids (dyads or triads). When the catalytic site is active, it may contain cysteine, histidine, aspartate or asparagine residues. As far as the metalloproteases are concerned, their active site is composed of a zinc ion and amino acids such as histidine, aspartate and serine. <ref>https://authors.library.caltech.edu/261/1/AMBpb04.pdf</ref> | |||
The studied structure shows both <scene name='86/868189/Catalytic_site_polyubiquitine/2'>the catalytic site (in orange) and polyubiquitine (in purple).</scene> | The studied structure shows both <scene name='86/868189/Catalytic_site_polyubiquitine/2'>the catalytic site (in orange) and polyubiquitine (in purple).</scene> | ||
Residues present in the catalytic site of DUBs are often in a '''non-functional orientation''' | Residues present in the catalytic site of DUBs are often in a '''non-functional orientation''' in the absence of substrate. As a result, when the substrate binds to the catalytic site of the enzyme, the site undergoes rearrangements and takes on a functional conformation. <ref>PMID:16537382</ref> The substrate opens and closes to allow the entry of the protein to be deubiquitinased. | ||
The enzyme | The enzyme takes this configuration thanks to <scene name='86/868189/H_bonds_around_ser177/1'>many hydrogen bonds around Ser177.</scene> This is why phosphorylation is so important to the function of the enzyme. The phosphate group forms many links between substrate ubiquitin and a segment of the OTU domain. This is rare among the known structures of deubiquitinases. Phosphorylation-driven conformational change resembles to the one of [https://en.wikipedia.org/wiki/Kinase kinases].<ref>PMID:22245969</ref> | ||
== Biological role == | == Biological role == | ||
DUBs are involved at multiple levels in the [[ubiquitin]] pathway. The modifications made by DUBs are post-translational modifications. Depending on the level, DUBs have different functions. Two specific cellular functions exist for deubiquitinases. They may act either on the degradation of the stabilization of a substrate in particular (réf 15 à ajoutées). Further functions are more specifically related to the ubiquitin molecule. Here are some of them : | |||
A : '''maturation of ubiquitin'''. When ubiquitin molecules are synthesized, they are not in free form. Thus, DUBs are essential for the generation of free monomers from precursors. The degradation of precursors is carried out by several DUBs belonging to the USPs class. | A : '''maturation of ubiquitin'''. When ubiquitin molecules are synthesized, they are not in free form. Thus, DUBs are essential for the generation of free monomers from precursors. The degradation of precursors is carried out by several DUBs belonging to the USPs class. | ||
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[[Image:DUBspathways.PNG |thumb|center|Figure 1 : Role of DUBs in the ubiquitin pathways]] | [[Image:DUBspathways.PNG |thumb|center|Figure 1 : Role of DUBs in the ubiquitin pathways]] | ||
Some other deubiquitinating enzymes also have biological functions. The latter are for instance involved in growth control, transcription silencing, regulation and viral infection or even the processing of ubiquitin-like-modifications. (réf 15 à ajoutées) | |||
== Disease == | == Disease == | ||
