Publications on protein domains
Stanislav Vershenya, Stefan Pinkert, Jörg Schultz
Abstract
Background
Results
Conclusions
Supplementary Online Material
List of all gene clusters of every pairwise comparison
Drosophila gambiae - Anopheles gambiae
Drosophila melanogaster - Apis Mellifera
Anopheles gambiae - Apis Mellifera
GO classification
GO Classification
Statistics
Chi Square Test Results
Stefan Pinkert, Jörg Schultz
Abstract
Background
Results
Conclusions
Supplementary Online Material
Detailed list of all novel domain architectures for each taxonomic group
Detailed list of all taxa with number of novel domain architectures with some/all/none occurrences of domains merged
tree like list of architectures(slow)
Chi_square test files
Birgit Pils, Jörg Schultz
J Mol Biol. 2004 Jul 9;340(3):399-404
Abstract
Although the catalytic center of an enzyme is usually highly conserved, there have been a few reports of proteins with substitutions at essential catalytic positions, which convert the enzyme into a catalytically inactive form. Here, we report a large-scale analysis of substitutions at enzymes' catalytic sites in order to gain insight into the function and evolution of inactive enzyme-homologues. Our analysis revealed that inactive enzyme-homologues are not an exception only found in single enzyme families, but that they are represented in a large variety of enzyme families and conserved among metazoan species. Even though they have lost their catalytic activity, they have adopted new functions and are now mainly involved in regulatory processes, as shown by several case studies. This modification of existing modules is an efficient mechanism to evolve new functions. The invention of inactive enzyme-homologues in metazoa has thereby led to an enhancement of complexity of regulatory networks.
Supplementary Online Material
Supplementary Online Material follows
Birgit Pils, Jörg Schultz
Mol Biol Evol. 2004 Apr;21(4):625-31
Abstract
The protein tyrosine phosphatase (PTP) family plays a central role in signal transduction pathways by controlling the phosphorylation state of serine, threonine, and tyrosine residues. PTPs can be divided into dual specificity phosphatases and the classical PTPs, which can comprise of one or two phosphatase domains. We studied amino acid substitutions at functional sites in the phosphatase domain and identified putative noncatalytic phosphatase domains in all subclasses of the PTP family. The presence of inactive phosphatase domains in all subclasses indicates that they were invented multiple times in evolution. Depending on the domain composition, loss of catalytic activity can result in different consequences for the function of the protein. Inactive single-domain phosphatases can still specifically bind substrate and protect it from dephosphorylation by other phosphatases. The inactive domains of tandem phosphatases can be further subdivided. The first class is more conserved, still able to bind phosphorylated tyrosine residues and might recruit multiphosphorylated substrates for the adjacent active domain. The second has accumulated several variable amino acid substitutions in the catalytic center, indicating a complete loss of tyrosine-binding capabilities. To study the impact of substitutions in the catalytic center to the evolution of the whole domain, we examined the evolutionary rates for each individual site and compared them between the classes. This analysis revealed a release of evolutionary constraint for multiple sites surrounding the catalytic center only in the second class, emphasizing its difference in function compared with the first class. Furthermore, we found a region of higher conservation common to both domain classes, suggesting a new regulatory center. We discuss the influence of evolutionary forces on the development of the phosphatase domain, which has led to additional functions, such as the specific protection of phosphorylated tyrosine residues, substrate recruitment, and regulation of the catalytic activity of adjacent domains.
Jörg Schultz, Birgit Pils
FEBS Lett. 2002 Oct 9;529(2-3):179-82
Abstract
N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase) is a key enzyme in the posttranslational modification of intracellular proteins by O-linked N-acetylglucosamine (O-GlcNAc). Here, we show that this protein contains two catalytic domains, one homologous to bacterial hyaluronidases and one belonging to the GCN5-related family of acetyltransferases (GNATs). Using sequence and structural information, we predict that the GNAT homologous region contains the O-GlcNAcase activity. Thus, O-GlcNAcase is the first member of the GNAT family not involved in transfer of acetyl groups, adding a new mode of evolution to this large protein family. Comparison with solved structures of different GNATs led to a reliable structure prediction and mapping of residues involved in binding of the GlcNAc-modified proteins and catalysis.
Torben Friedrich, Birgit Pils, Thomas Dandekar, Jörg Schultz, Tobias Müller
Abstract
Motivation:
Due to the growing number of completely sequenced genomes, functional
annotation of proteins becomes a more and more important issue. Here, we
describe a method for the prediction of sites within protein domains, which are
part of protein-ligand interactions. As recently demonstrated these sites are
not trivial to detect because of a varying degree of conservation of their
location and type within a domain family.
Results:
The developed method for the prediction of protein-ligand interaction sites is
based on a newly defined interaction profile hidden Markov model (ipHMM)
topology that takes structural and sequence data into account. It is based on a
homology search via a posterior decoding algorithm that yields probabilities
for interacting sequence positions and inherits the efficiency and the power of
the profile HMM methodology. The algorithm enhances the quality of interaction
site predictions and is a suitable tool for large scale studies, which was
already demonstrated for profile HMMs.
Supplementary Online Material
Table S1: Cross Validation Results of Peptide-ligand ipHMMs
Table S2: Cross Validation Results of Ion-ligand ipHMMs
Table S3: Cross Validation Results of Nucleotide-ligand ipHMMsl
Table S4: Validation Results of Peptide-ligand ipHMMs using generated Sequences
Table S5: Validation Results of Ion-ligand ipHMMs using generated Sequences
Table S6: Validation Results of Nucleotide-ligand ipHMMs using generated Sequencese
Table S7: ROC and Cross-validation Results of ipHMMs
Table S8: BLAST-based interaction site prediction
Table S9: Distribution of Peptide-Ligand Sequences over Domains
Table S10: Distribution of Nucleotide-Ligand Sequences over Domains
Table S11: Distribution of Ion-Ligand Sequences over Domains
Table S12: Histograms of Sequence Distribution over Domains
Jörg Schultz Corresponding author
Tobias Müller
Birgit Pils
Stanislav Vershenya
Stefan Pinkert
Torben Friedrich