Medical Research Council

David Komander

Dario Alessi

Ricardo Biondi

Manuela K Hospenthal

Tycho E T Mevissen

Daan Van Aalten

Anja Bremm

Yu Ye

There is described a method for analyzing ubiquitin polymers using linkage-specific deubiquitinase enzymes. Novel specificities of deubiquitinase enzymes are also provided.

Ubiquitin chain analysis

The invention provides a chimeric E2 enzyme comprising a Ubc domain fused to a heterologous ubiquitin binding domain (UBD). The chimeric enzymes of the invention may be useful in producing elevated levels of free polyubiquitin.

Engineered E2 for increasing the content of free LYS11-linked ubiquitin

A method for selecting a compound for modulating the activity of phosphoinositide dependent protein kinase 1 (PDKI) is provided. The method may comprise modelling a three dimensional structure of a plurality of molecules in a computer, comparing with the three dimensional structure of the compounds with that of a reference structure such as at least part of a protein kinase catalytic domain of PDK1, and selecting the compound based on a predicted interacting ability of the molecules to the protein kinase catalytic domain. Also a method for selecting a compound for modulating the activity of hydrophobic pocket containing protein kinase is provided. In this method, the reference structures may be one or more of a phosphate binding pocket of PDK1, a hydrophobic pocket of PDK1, and &#x3b1;C helix or region interacting therewith of PDK1.

Method for designing a compound based on the three dimensional structure of phosphoinositide dependent protein kinase 1 (PDK1)

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Cambridge, United Kingdom

David Komander