Insights into the evolution of protein domains give rise to improvements of function prediction
type: CreativeWork
description: The growing number of uncharacterised sequences in public databases has turned the prediction of protein function into a challenging research field. Traditional annotation methods are often error-prone due to the small subset of proteins with experimentally verified function. Goal of this thesis was to analyse the function and evolution of protein domains in order to understand molecular processes in the cell. The focus was on signalling domains of little understood function, as well as on functional sites of protein domains in general. Glucosaminidases (GlcNAcases) represent key enzymes in signal transduction pathways. Together with glucosamine transferases, they serve as molecular switches, similar to kinases and phosphatases. Little was known about the molecular function and structure of the GlcNAcases. In this thesis, the GlcNAcases were identified as remote homologues of N-acetyltransferases. By comparing the homologous sequences, I was able to predict functional sites of the GlcNAcase family and to identify the GlcNAcases as the first family member of the acetyltransferase superfamily with a distinct catalytic mechanism, which is not involved in the transfer of acetyl groups. In a similar approach, the sensor domain of a plant hormone receptor was studied. I was able to predict putative ligand-binding sites by comparing evolutionary constraints in functionally diverged subfamilies. Most of the putative ligand-binding sites have been experimentally confirmed in the meantime. Due to the importance of enzymes involved in cellular signalling, it seems impossible to find substitutions of catalytic amino acids that turn them catalytically inactive. Nevertheless, by scanning catalytic positions of the protein tyrosine phosphatase families, I found many inactive domains among single domain and tandem domain phosphatases in metazoan proteomes. In addition, I found that inactive phosphatases are conserved throughout evolution, which led to the question about the functio…
abstract: The growing number of uncharacterised sequences in public databases has turned the prediction of protein function into a challenging research field. Traditional annotation methods are often error-prone due to the small subset of proteins with experimentally verified function. Goal of this thesis was to analyse the function and evolution of protein domains in order to understand molecular processes in the cell. The focus was on signalling domains of little understood function, as well as on functional sites of protein domains in general. Glucosaminidases (GlcNAcases) represent key enzymes in signal transduction pathways. Together with glucosamine transferases, they serve as molecular switches, similar to kinases and phosphatases. Little was known about the molecular function and structure of the GlcNAcases. In this thesis, the GlcNAcases were identified as remote homologues of N-acetyltransferases. By comparing the homologous sequences, I was able to predict functional sites of the GlcNAcase family and to identify the GlcNAcases as the first family member of the acetyltransferase superfamily with a distinct catalytic mechanism, which is not involved in the transfer of acetyl groups. In a similar approach, the sensor domain of a plant hormone receptor was studied. I was able to predict putative ligand-binding sites by comparing evolutionary constraints in functionally diverged subfamilies. Most of the putative ligand-binding sites have been experimentally confirmed in the meantime. Due to the importance of enzymes involved in cellular signalling, it seems impossible to find substitutions of catalytic amino acids that turn them catalytically inactive. Nevertheless, by scanning catalytic positions of the protein tyrosine phosphatase families, I found many inactive domains among single domain and tandem domain phosphatases in metazoan proteomes. In addition, I found that inactive phosphatases are conserved throughout evolution, which led to the question about the functio…
author: Pils, Birgit
keywords: Protein, Domäne, Funktionelle Positionen, Bioinformatik, Evolution, Domain, Functional Sites, Bioinformatics
date published: 2006-02-08
date modified: 2026-07-24T06:11:49Z
provider: Universität Wüzburg
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universität Würzburg