Hubbard, Simon Jeremy;
(1992)
Analysis of protein-protein molecular recognition.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The molecular recognition exhibited between particular protein molecules has been analyzed, utilising the Brookhaven databank of atomic resolution protein structures. Specifically, an extensive study of the recognition between serine proteinases, and their protein inhibitors and substrates has been made. The analyses involve comparisons of the molecular structure of these protein inhibitors, specifically at their recognition regions, and further comparisons with protein substrates of the proteinases. These comparisons reveal a common recognition motif possessed by the binding loops of serine proteinase inhibitors, which is absent in the substrates (limited proteolytic sites). This conserved recognition motif is maintained despite the sequence and global structural dissimilarity between inhibitor families. In contrast, the recognition regions of the substrates are structurally diverse, and could not be bound to their target enzymes in their crystal conformations. This implies mobility is vital for their recognition, to allow structural rearrangement. Modelling experiments are carried out to ascertain the degree to which the limited proteolytic sites may adopt inhibitor-like conformations, thus mimicking the expected recognition conformation. This was done by first testing the ability of the substrates to adopt such a conformation geometrically, and secondly to simulate the types of motions that might occur. Finally, an algorithm is presented that predicts the likely location of limited proteolytic sites within proteins. The predictive power of the method and its individual component parameters are critically assessed.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Analysis of protein-protein molecular recognition |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest |
| Keywords: | Pure sciences; Protein inhibitors |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10111910 |
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