Hydrolytic cleavage of peptide bonds is an energetically· favorable reaction, but one that normally takes place very slowly at room temperature, even in the presence of rather strong acids or bases. It can be strongly cataly~ed by many proteases, and much effort has been expended to determine how these· have the ability to increase the rate of hydrolysis by a million-fol.d or more in neutral so...

Asparaginyl endopeptidase (AEP), also known as legumain, is a cysteine protease that has been ascribed roles in antigen presentation yet its exact role in human biology remains poorly understood. We report here, the use of a positional scanning combinatorial library of peptide AOMKs containing a P1 aspartic acid to probe the P2, P3, and P4 subsite specificity of endogenous legumain. Using inhib...

The linear interaction energy (LIE) method is combined with energy minimization and finite-difference Poisson calculation of electrostatic solvation for the estimation of the absolute free energy of binding. A predictive accuracy of about 1.0 kcal/mol is obtained for 13 and 29 inhibitors of beta-secretase (BACE) and HIV-1 protease (HIV-1 PR), respectively. The multiplicative coefficients for th...

A chromosomal DNA of Scytalidium lignicolum was digested with Sau3AI. The digest was self-ligated and amplified by inverse PCR procedure using primers designed based on the nucleotide sequences of up- and down-stream regions of an intron present in the scytalidopepsin B gene. Analysis of the nucleotide sequence of PCR product (700 bp) showed that the enzyme is synthesized as a precursor protein...

Mempasin 2, a beta-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of beta-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been esta...

The data described here supports the research article "Unraveling HIV Protease Flaps Dynamics by Constant pH Molecular Dynamics Simulations" (Soares et al., 2016) [1]. The data involves both standard Molecular Dynamics (MD) and Constant pH Molecular Dynamics (CpHMD) to elucidate the effect of protonation states of catalytic dyad on the HIV-PR conformation. The data obtained from MD simulation d...

Nelfinavir mesylate (formerly AG1343) is a potent and selective inhibitor of human immunodeficiency virus (HIV) protease approved for the treatment of individuals infected with HIV. Nucleotide sequence analysis of protease genes from plasma HIV type 1 (HIV-1) RNA revealed a unique aspartic acid (D)-to-asparagine (N) substitution at residue 30 (D30N) in 25 of 55 patients treated with nelfinavir ...

Dendritic cells (DC) of the CD11c(+) myeloid phenotype have been implicated in the spread of scrapie in the host. Previously, we have shown that CD11c(+) DC can cause a rapid degradation of proteinase K-resistant prion proteins (PrP(Sc)) in vitro, indicating a possible role of these cells in the clearance of PrP(Sc). To determine the mechanisms of PrP(Sc) degradation, CD11c(+) DC that had been ...

The filamentous fungus Trichoderma reesei has tremendous capability to secrete proteins. Therefore, it would be an excellent host for producing high levels of therapeutic proteins at low cost. Developing a filamentous fungus to produce sensitive therapeutic proteins requires that protease secretion is drastically reduced. We have identified 13 major secreted proteases that are related to degrad...