A server and database for dipole moments of proteins

An Internet server at http://bip.weizmann.ac.il/dipol calculates the net charge, dipole moment and mean radius of any 3D protein structure or its constituent peptide chains, and displays the dipole vector superimposed on a ribbon backbone of the protein. The server can also display the angle between the dipole and a selected list of amino acid residues in the protein. When the net charges and dipole moments of ∼12 000 non-homologous PDB biological units (PISCES set), and their unique chains of length 50 residues or longer, were examined, the great majority of both charges and dipoles fell into a very narrow range of values, with long extended tails containing a few extreme outliers. In general, there is no obvious relation between a protein's charge or dipole moment and its structure or function, so that its electrostatic properties are highly specific to the particular protein, except that the majority of chains with very large positive charges or dipoles bind to ribosomes or interact with nucleic acids

Proteopedia - a scientific 'wiki' bridging the rift between three-dimensional structure and function of biomacromolecules

Proteopedia is an interactive wiki-style web resource that presents 3D structural and functional information in a user-friendly manner and allows real-time community annotation

Control of the rate of evaporation in protein crystallization by the ‘microbatch under oil’ method

A procedure is presented for controlling the rate of evaporation during ‘microbatch under oil’ protein crystallization

An idea whose time has come

A response to An idea whose time has gone by Gregory A Petsko, Genome Biology 2007, 8:107

FoldIndex©: a simple tool to predict whether a given protein sequence is intrinsically unfolded

Summary: An easy-to-use, versatile and freely available graphic web server, FoldIndex© is described: it predicts if a given protein sequence is intrinsically unfolded implementing the algorithm of Uversky and co-workers, which is based on the average residue hydrophobicity and net charge of the sequence. FoldIndex© has an error rate comparable to that of more sophisticated fold prediction methods. Sliding windows permit identification of large regions within a protein that possess folding propensities different from those of the whole protein. Availability: FoldIndex© can be accessed at http://bioportal.weizmann.ac.il/fldbin/findex Contact: [email protected] Supplementary information: http://www.weizmann.ac.il/sb/faculty_pages/Sussman/papers/suppl/Prilusky_200

Cyclodextrin-mediated Crystallization of Acid β-glucosidase in Complex with Amphiphilic Bicyclic Nojirimycin Analogues

Cyclodextrin-based host-guest chemistry has been exploited to facilitate co-crystallization of recombinant human acid β-glucosidase (β-glucocerebrosidase, GlcCerase) with amphiphilic bicyclic nojirimycin analogues of the sp2-iminosugar type. Attempts to co-crystallize GlcCerase with 5-N,6-O-[N′-(n-octyl)iminomethylidene]nojirimycin (NOI-NJ) or with 5-N,6-S-[N′-(n-octyl)iminomethylidene]-6-thionojirimycin (6S-NOI-NJ), two potent inhibitors of the enzyme with promising pharmacological chaperone activity for several Gaucher disease-associated mutations, were unsuccessful probably due to the formation of aggregates that increase the heterogeneity of the sample and affect nucleation and growth of crystals. Cyclomaltoheptaose (β-cyclodextrin, βCD) efficiently captures NOI-NJ and 6S-NOI-NJ in aqueous media to form inclusion complexes in which the lipophilic tail is accommodated in the hydrophobic cavity of the cyclooligosaccharide. The dissociation constant of the complex of the amphiphilic sp2-iminosugars with βCD is two orders of magnitude higher than that of the corresponding complex with GlcCerase, allowing the efficient transfer of the inhibitor from the βCD cavity to the GlcCerase active site. Enzyme-inhibitor complexes suitable for X-ray analysis were thus grown in the presence of βCD. In contrast to what was previously observed for the complex of GlcCerase with the more basic derivative, 6-amino-6-deoxy-5-N,6-N-[N′-(n-octyl)iminomethylidene]nojirimycin (6N-NOI-NJ), the β-anomers of both NOI-NJ and 6S-NOI-NJ were seen in the active site, even though the α-anomer was exclusively detected both in aqueous solution and in the corresponding βCD:sp2-iminosugar complexes. Our results further suggest that cyclodextrin derivatives might serve as suitable delivery systems of amphiphilic glycosidase inhibitors in a biomedical context.Ministerio de Ciencia e Innovación CTQ2007-61180/PPQ, SAF2010-15670, CTQ2010-15848Junta de Andalucía P08-FQM-03711Fondo Europeo de Desarrollo Regional 03122, ISSG-CT-2007-03719

The α/β hydrolase fold

We have identified a new protein fold-the α/β hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an α/β sheet, not barrel, of eight β-sheets connected by α-helices. These enzymes have diverged from a common ancestor so as to preserve the arrangement of the catalytic residues, not the binding site. They all have a catalytic triad, the elements of which are borne on loops which are the best-conserved structural features in the fold. Only the histidine in the nucleophile-histidine-acid catalytic triad is completely conserved, with the nucleophile and acid loops accommodating more than one type of amino acid. The unique topological and sequence arrangement of the triad residues produces a catalytic triad which is, in a sense, a mirror-image of the serine protease catalytic triad. There are now four groups of enzymes which contain catalytic triads and which are related by convergent evolution towards a stable, useful active site: the eukaryotic serine proteases, the cysteine proteases, subtilisins and the α/β hydrolase fold enzymes