Summary: Iterative similarity searches with PSI-BLAST position-specific score matrices (PSSMs) find many more homologs than single searches, but PSSMs can be contaminated when homologous alignments are extended into unrelated protein domains—homologous over-extension (HOE). PSI-Search combines an optimal Smith–Waterman local alignment sequence search, using SSEARCH, with the PSI-BLAST profile construction strategy. An optional sequence boundary-masking procedure, which prevents alignments from being extended after they are initially included, can reduce HOE errors in the PSSM profile. Preventing HOE improves selectivity for both PSI-BLAST and PSI-Search, but PSI-Search has ~4-fold better selectivity than PSI-BLAST and similar sensitivity at 50% and 60% family coverage. PSI-Search is also produces 2- for 4-fold fewer false-positives than JackHMMER, but is ~5% less sensitive.

Availability and implementation: PSI-Search is available from the authors as a standalone implementation written in Perl for Linux-compatible platforms. It is also available through a web interface (www.ebi.ac.uk/Tools/sss/psisearch) and SOAP and REST Web Services (www.ebi.ac.uk/Tools/webservices).

Contact: pearson@virginia.edu; rodrigo.lopez@ebi.ac.uk

X-ray crystallographic analysis with Cu Kα radiation established the relative configurations of the stereogenic centers in the title compound, C15H20N2O5, and clarified mechanistic ambiguities in the synthesis. The conformation of the five-membered ring approximates twisted, about a C—O bond. The absolute configuration of this carbon-branched dipeptide isostere was known based on the use of d-ribose as the starting material. Refinement of the Flack parameter gave an ambiguous result but the refined Hooft parameter is in agreement with the assumed (d-ribose) absolute structure. The crystal structure consists of N—H⋯O and O—H⋯O hydrogen-bonded bi-layers, with the terminal methyl and phenyl groups forming a hydro­phobic inter-layer inter­face. Some weak C—H⋯O inter­actions are also present.

The title compound, C21H26O10S, was synthesized in a single step from mannose penta­acetate. The mol­ecular structure confirms the α configuration of the anomeric thioaryl substituent. Spectroscopic and melting-point data obtained for the title compound are in disagreement with those previously reported, indicating the previously reported synthesis [Durette & Shen (1980 ▶). Carbohydr. Res. 81, 261–274] to be erroneous. The crystal structure is stabilized by weak inter­molecular C—H⋯O hydrogen bonds.

The Kiliani reaction on 1-de­oxy-(N,N-dimethyl­amino)-d-fructose, itself readily available from reaction of dimethyl­amine and d-glucose, proceeded to give access to the title β-sugar amino acid, C15H27NO7. X-ray crystallography determined the stereochemistry at the newly formed chiral center. There are two mol­ecules in the asymmetric unit; they are related by a pseudo-twofold rotation axis and have very similar geometries, differing only in the conformation of one of the acetonide rings. All the acetonide rings adopt envelope conformations; the flap atom is oxygen in three of the rings, but carbon in one of them. There are two strong hydrogen bonds between the two independent mol­ecules, and further weak hydrogen bonds link the mol­ecules to form infinite chains running parallel to the a axis.

The title compound, C40H31NO11S·0.53CH2Cl2·0.38C4H10O, was synthesized in two steps from mannose penta­acetate and single crystals were grown by slow evaporation. The structure was determined by single-crystal X-ray diffraction, confirming the α-configuration of the anomeric thioaryl substituent. The asymmetric unit contains two crystallographically distinct mol­ecules of the carbohydrate. The central pyran­ose rings of these are geometrically similar, but there are differences in the orientations of the benzoate substituents.