Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Initial cleavage sites of native insulin at a pH of about 3 and stereospecificity were investigated by fungal carboxyl proteinases (EC 3.4.23.6) from ASpergillus sojae, a species of fungi imperfecti, and Pycnoporus coccineus (formerly designated Trametes sanguinea), a wood deteriorating Basidiomycete, respectively. Fungal carboxyl proteinases were used as a model of vertebrate insulin degradation. A. sojae carboxyl proteinase I primarily hydrolyzed two peptide bonds located on the surface of native insulin monomer, the B16-B17 (Tyr-Leu) and B24-B25 (Phe-Phe) bonds, and secondarily the buried bonds, A15-A16 (Gln-Leu), B15-B16 (Leu-Tyr) and B14-B15 (ala-Leu), at pH 3.2 and 30 degree C. The initial cleavage sites of A. sojae carboxyl proteinases I towards native insulin were not identical with the initial cleavage sites towards the oxidized B chain of insulin. P. coccineus carboxyl proteinase Ia selectively hydrolyzed B14-B15 (Ala-Leu), B16-B17 (Tyr-Leu) and B24-B25 (Phe-Phe) bonds in the native insulin at pH 2.7. Based on these findings we suggest that the stereospecificity of the fungal carboxyl proteinases is similar to that of cathepsin D (EC 3.4.23.5), and that the synthesis and degradation of insulin may occur in microorganisms.
 ...
PMID:Initial sites of insulin cleavage and stereospecificity of carboxyl proteinases from Aspergillus sojae and Pycnoporus coccineus. 703 82

Plasmepsins (Plm) II (EC number: 3.4.23.39) and IV (EC number: 3.4.23.B14) are aspartic proteases present in the food vacuole of the malaria parasite Plasmodium falciparum and are involved in host hemoglobin degradation. Based on our established efficient synthetic sequence, a series of inhibitors for Plm II and IV has been synthesized bearing a 2,3,4,7-tetrahydro-1H-azepine scaffold as the core structural element. During the computational design cycle, thorough investigations were carried out in order to find a reasonable theoretical binding mode for Plm II and IV. The conformation of Plm II in the crystal structure (PDB code: 1LF2) provides a good starting geometry for our virtual screening approach. In contrast, the only available co-crystal structure for Plm IV of P. falciparum (PDB code: 1LS5) appears inappropriate for inhibitor design. Therefore, a homology model was constructed based on the Plm II 1LF2 structure. A combinatorial docking run using FlexX(c) suggested compounds which, after synthesis, turned out to exhibit affinities in the sub-micromolar range. The observed structure-activity relationships of the synthesized compounds confirm the assumed binding mode for Plm II and IV. The best-binding inhibitors designed for Plm II and IV are devoid of any inhibitory potency against human cathepsin D (EC number: 3.4.23.5).
 ...
PMID:Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors. 1875 22