SERPENT—an information storage and analysis resource for protein sequences

Akrigg, D.; Attwood, Terri; Bleasby, Alan J.; Findlay, John B. C.; North, A. C. T.; Maughan, N. A.; Parry‐Smith, David J.; Perkins, David N.; Wootton, John C.

doi:10.1093/bioinformatics/8.3.295

Cited by 18 publications

(11 citation statements)

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“…Comparisons of protein structure were undertaken by visual inspection and manipulation of coordinates using the interactive computer graphics program FRODO (Jones, 1985). Sequence analysis was conducted using the ADSP system, part of the SERPENT package (Akrigg et al, 1992); the methodology and working principles of ADSP have recently been described in detail by ParrySmith and Attwood (1992). Hitlists of the top 500 sequences were used in all cases.…”

Section: Methodsmentioning

confidence: 99%

Structure and sequence relationships in the lipocalins and related proteins

1993

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The lipocalins and fatty acid-binding proteins (FABPs) are two recently identified protein families that both function by binding small hydrophobic molecules. We have sought to clarify relationships within and between these two groups through an analysis of both structure and sequence. Within a similar overall folding pattern, we find large parts of the lipocalin and FABP structures to be quantitatively equivalent. The three largest structurally conserved regions within the lipocalin common core correspond to characteristic sequence motifs that we have used to determine the constitution of this family using an iterative sequence analysis procedure. This afforded a new interpretation of the family, which highlighted the difficulties of determining a comprehensive and coherent classification of the lipocalins. The first of the three conserved sequence motifs is also common to the FABPs and corresponds to a conserved structural element characteristic of both families. Similarities of structure and sequence within the two families suggests that they form part of a larger "structural superfamily"; we have christened this overall group the calycins to reflect the cup-shaped structure of its members.

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Section: Methodsmentioning

confidence: 99%

Structure and sequence relationships in the lipocalins and related proteins

1993

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“…Protein sequences were extracted from the OWL compiled, nonredundant protein sequence database (Bleasby and Wootton 1990;Akrigg et al 1992). Homology between the protein sequences was investigated using a PC implementation of DIAGON (Giles 1984).…”

Section: Methodsmentioning

confidence: 99%

A fungal phylogeny based upon orotidine 5?-monophosphate decarboxylase

Radford

1993

J Mol Evol

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Orotidine 5'-monophosphate decarboxylase protein sequences from 14 fungi, 1 slime mold, 2 mammals, and 3 bacteria are compared and aligned and shown to be homologous. Based on the optimal alignment of the fungal sequences, a phylogenetic tree is derived. Within the fungi, the fission yeast Schizosaccharomyces pombe shows a closer relationship to both basidiomycetes and phycomycetes than it does to orthodox ascomycetes (plectomycetes, pyrenomycetes, and budding yeasts). Intron conservation shows a close relationship between phycomycetes and basidiomycetes. The imperfect fungi Trichoderma and Cephalosporium are shown to be closely related to Neurospora. The predicted origin of the group of budding yeasts is dependent on the analytical method used.

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“…BIPED [47,48] and SESAM [49] are the first examples of operational relational protein sequence and structure databases. They are both based on commercial, general, relational database management systems.…”

Section: Model Building By Homology and Design Of Site-directed Mutatmentioning

confidence: 99%

Prediction and analysis of structure, stability and unfolding of thermolysin-like proteases

Vriend¹,

Eijsink²

1993

J Computer-Aided Mol Des

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Bacillus neutral proteases (NPs) form a group of well-characterized homologous enzymes, that exhibit large differences in thermostability. The three-dimensional (3D) structures of several of these enzymes have been modelled on the basis of the crystal structures of the NPs of B. thermoproteolyticus (thermolysin) and B. cereus. Several new techniques have been developed to improve the model-building procedures. Also a 'model-building by mutagenesis' strategy was used, in which mutants were designed just to shed light on parts of the structures that were particularly hard to model. The NP models have been used for the prediction of site-directed mutations aimed at improving the thermostability of the enzymes. Predictions were made using several novel computational techniques, such as position-specific rotamer searching, packing quality analysis and property-profile database searches. Many stabilizing mutations were predicted and produced: improvement of hydrogen bonding, exclusion of buried water molecules, capping helices, improvement of hydrophobic interactions and entropic stabilization have been applied successfully. At elevated temperatures NPs are irreversibly inactivated as a result of autolysis. It has been shown that this denaturation process is independent of the protease activity and concentration and that the inactivation follows first-order kinetics. From this it has been conjectured that local unfolding of (surface) loops, which renders the protein susceptible to autolysis, is the rate-limiting step. Despite the particular nature of the thermal denaturation process, normal rules for protein stability can be applied to NPs. However, rather than stabilizing the whole protein against global unfolding, only a small region has to be protected against local unfolding. In contrast to proteins in general, mutational effects in proteases are not additive and their magnitude is strongly dependent on the location of the mutation. Mutations that alter the stability of the NP by a large amount are located in a relatively weak region (or more precisely, they affect a local unfolding pathway with a relatively low free energy of activation). One weak region, that is supposedly important in the early steps of NP unfolding, has been determined in the NP of B. stearothermophilus. After eliminating this weakest link a drastic increase in thermostability was observed and the search for the second-weakest link, or the second-lowest energy local unfolding pathway is now in progress. Hopefully, this approach can be used to unravel the entire early phase of unfolding.

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SERPENT—an information storage and analysis resource for protein sequences

Cited by 18 publications

References 0 publications

Structure and sequence relationships in the lipocalins and related proteins

Structure and sequence relationships in the lipocalins and related proteins

A fungal phylogeny based upon orotidine 5?-monophosphate decarboxylase

Prediction and analysis of structure, stability and unfolding of thermolysin-like proteases

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