a-70450 and pepstatin

a-70450 has been researched along with pepstatin* in 2 studies

Other Studies

2 other study(ies) available for a-70450 and pepstatin

ArticleYear
The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors.
    Structure (London, England : 1993), 1995, Nov-15, Volume: 3, Issue:11

    Infections caused by Candida albicans, a common fungal pathogen of humans, are increasing in incidence, necessitating development of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is considered an important virulence factor in these infections and might offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form expressed in a number of C. albicans strains.. The three-dimensional structures of SAP2 complexed with the tight-binding inhibitor A70450 (a synthetic hexapeptide analogue) and with the general aspartic proteinase inhibitor pepstatin A (a microbial natural product) have been determined to 2.1 A and 3.0 A resolution, respectively. Although the protein structure retains the main features of a typical aspartic proteinase, it also shows some significant differences, due mainly to several sequence insertions and deletions (as revealed by homology modelling), that alter the shape of the binding cleft. There is also considerable variation in the C-terminal structural domain.. The differences in side chains, and in the conformations adopted by the two inhibitors, particularly at their P4, P3 and P'2 positions (using standard notation for protease-inhibitor residues), allows the A70450 structure to complement, more accurately, that of the substrate-binding site of SAP2. Some differences in the binding clefts of other SAP isoenzymes may be deduced from the SAP2 structure.

    Topics: Amino Acid Sequence; Antifungal Agents; Aspartic Acid Endopeptidases; Binding Sites; Candida albicans; Crystallography, X-Ray; Drug Design; Enzyme Inhibitors; Fungal Proteins; Isoenzymes; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; Pepstatins; Piperazines; Protein Binding; Protein Conformation; Sequence Alignment; Sequence Homology, Amino Acid

1995
Crystallization of inhibited aspartic proteinase from Candida albicans.
    Journal of molecular biology, 1993, Dec-20, Volume: 234, Issue:4

    A major secreted aspartic proteinase from Candida albicans has been crystallized in the presence of inhibitors to prevent autodegradation. With pepstatin a cleaved form of the enzyme was nevertheless found in the crystals whereas with the inhibitor A70450 the enzyme remained intact. The crystals containing pepstatin were not suitable for X-ray data collection while the crystals containing A70450 grew by vapour diffusion as tetragonal bipyramids, space group P4(3)2(1)2 (or P4(1)2(1)2), a = b = 76.2 A, c = 126.1 A, with one molecule in the asymmetric unit and they diffract to beyond 2.2 A.

    Topics: Aspartic Acid Endopeptidases; Candida albicans; Crystallography, X-Ray; Models, Molecular; Pepstatins; Piperazines; Protein Structure, Tertiary

1993