16 research outputs found
The PE-PPE Domain in Mycobacterium Reveals a Serine α/β Hydrolase Fold and Function: An In-Silico Analysis
The PE and PPE proteins first reported in the genome sequence of Mycobacterium tuberculosis strain H37Rv are now identified in all mycobacterial species. The PE-PPE domain (Pfam ID: PF08237) is a 225 amino acid residue conserved region located towards the C-terminus of some PE and PPE proteins and hypothetical proteins. Our in-silico sequence analysis revealed that this domain is present in all Mycobacteria, some Rhodococcus and Nocardia farcinica genomes. This domain comprises a pentapeptide sequence motif GxSxG/S at the N-terminus and conserved amino acid residues Ser, Asp and His that constitute a catalytic triad characteristic of lipase, esterase and cutinase activity. The fold prediction and comparative modeling of the 3-D structure of the PE-PPE domain revealed a “serine α/β hydrolase” structure with a central β-sheet flanked by α-helices on either side. The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site. The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified. Our findings add to the growing list of serine hydrolases in mycobacterium, which are essential for the maintenance of their impermeable cell wall and virulence. These results provide the directions for the design of experiments to establish the function of PE and PPE proteins
Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria
Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found
Primary Research Paper Identification and analysis of novel tandem repeats in the cell surface proteins of archaeal and bacterial genomes using computational tools
Abstract We have identified four novel repeats and two domains in cell surface proteins encoded by the Methanosarcina acetivorans genome and in some archaeal and bacterial genomes. The repeats correspond to a certain number of amino acid residues present in tandem in a protein sequence and each repeat is characterized by conserved sequence motifs. These correspond to: (a) a 42 amino acid (aa) residue RIVW repeat; (b) a 45 aa residue LGxL repeat; (c) a 42 aa residue LVIVD repeat; and (d) a 54 aa residue LGFP repeat. The domains correspond to a certain number of aa residues in a protein sequence that do not comprise internal repeats. These correspond to: (a) a 200 aa residue DNRLRE domain; and (b) a 70 aa residue PEGA domain. We discuss the occurrence of these repeats and domains in the different proteins and genomes analysed in this work
Profile-Based Summarisation for Web Site Navigation
Information systems that utilise contextual information have the potential of helping a user identify relevant information more quickly and more accurately than systems that work the same for all users and contexts. Contextual information comes in a variety of types, often derived from records of past interactions between a user and the information system. It can be individual or group based. We are focusing on the latter, harnessing the search behaviour of cohorts of users, turning it into a domain model that can then be used to assist other users of the same cohort. More specifically, we aim to explore how such a domain model is best utilised for
profile-biased summarisation
of documents in a
navigation
scenario in which such summaries can be displayed as hover text as a user moves the mouse over a link. The main motivation is to help a user find relevant documents more quickly. Given the fact that the
Web
in general has been studied extensively already, we focus our attention on
Web sites
and similar document collections. Such collections can be notoriously difficult to search or explore. The process of acquiring the domain model is not a research interest here; we simply adopt a biologically inspired method that resembles the idea of ant colony optimisation. This has been shown to work well in a variety of application areas. The model can be built in a continuous learning cycle that exploits search patterns as recorded in typical query log files. Our research explores different summarisation techniques, some of which use the domain model and some that do not. We perform task-based evaluations of these different techniques—thus of the impact of the domain model and profile-biased summarisation—in the context of Web site navigation.
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