Alla Gustchina

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BACKGROUND Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological(More)
Kinetic analysis and modeling studies of HIV-1 and HIV-2 proteinases were carried out using the oligopeptide substrate [formula: see text] and its analogs containing single amino acid substitutions in P3-P3' positions. The two proteinases acted similarly on the substrates except those having certain hydrophobic amino acids at P2, P1, P2', and P3' positions(More)
Retroviral proteases form a unique subclass of the family of aspartic proteases. These homodimeric enzymes from a number of viral sources have by now been extensively characterized, both structurally and biochemically. The importance of such knowledge to the development of new drugs against AIDS has been, to a large extent, the driving force behind this(More)
The successful development of a number of HIV-1 protease (PR) inhibitors for the treatment of AIDS has validated the utilization of retroviral PRs as drug targets and necessitated their detailed structural study. Here we report the structure of a complex of human T cell leukemia virus type 1 (HTLV-1) PR with a substrate-based inhibitor bound in subsites P5(More)
ATP-dependent Lon protease degrades specific short-lived regulatory proteins as well as defective and abnormal proteins in the cell. The crystal structure of the proteolytic domain (P domain) of the Escherichia coli Lon has been solved by single-wavelength anomalous dispersion and refined at 1.75-A resolution. The P domain was obtained by chymotrypsin(More)
ATP-dependent Lon proteases belong to the superfamily of AAA+ proteins. Until recently, the identity of the residues involved in their proteolytic active sites was not elucidated. However, the putative catalytic Ser-Lys dyad was recently suggested through sequence comparison of more than 100 Lon proteases from various sources. The presence of the catalytic(More)
ATP-dependent Lon proteases are multi-domain enzymes found in all living organisms. All Lon proteases contain an ATPase domain belonging to the AAA(+) superfamily of molecular machines and a proteolytic domain with a serine-lysine catalytic dyad. Lon proteases can be divided into two subfamilies, LonA and LonB, exemplified by the Escherichia coli and(More)
The proteases of retroviruses, such as leukemia viruses, immunodeficiency viruses (including the human immunodeficiency virus, HIV), infectious anemia viruses, and mammary tumor viruses, form a family with the proteases encoded by several retrotransposons in Drosophila and yeast and endogenous viral sequences in primates. Retroviral proteases are key(More)
In order to study the relationships of aspartic proteases, we have modified pepsin, a single-chain eukaryotic enzyme, to a two-chain heterodimer, which resembles aspartic proteases from retrovirus, including human immunodeficiency virus. Two fragments of pepsinogen, residues 1P-172 and 173-326, were expressed separately in Escherichia coli. Mixtures of(More)
The sequence requirements for HIV-1 proteinase catalyzed cleavage of oligopeptides containing two distinct types of junctions (-hydrophobic*hydrophobic- or -aromatic*Pro-) has been investigated. For the first type of junction (-hydrophobic*hydrophobic-) the optimal residues in the P2 and P2' positions were found to be Val and Glu, respectively, in accord(More)