The dimeric form of bacterial l-asparaginase YpAI is fully active.

l-asparaginases from mesophilic bacteria (ASNases), including two enzymes very successfully used in the treatment of leukaemia, have been consistently described as homotetramers. On the contrary, structural studies show that homodimers of these enzymes should be sufficient to carry out the catalytic reaction. In this report, we investigated whether the type I Yersinia pestis asparaginase (YpAI) is active in a dimeric form or whether the tetrameric quaternary structure is critical for its activity.

Human β-defensin 4 - defensin without the "twist".

β-defensins are small, cysteine-rich, cationic peptides that contribute to various processes related to both arms of host defense, the innate and adaptive immunities. All β-defensins are potent antimicrobials with activity targeting a broad range of pathogens. Some human β-defensins (hBDs) are also capable of binding and activating specific chemokine receptors, leading to chemotaxis of receptor-presenting cells.

Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis.

Background: We applied crosslinking techniques as a first step in preparation of stable avian sarcoma virus (ASV) integrase (IN)-DNA complexes for crystallographic investigations. These results were then compared with the crystal structures of the prototype foamy virus (PFV) intasome and with published data for other retroviral IN proteins.

Methodology/results: Photoaffinity crosslinking and site-directed chemical crosslinking were used to localize the sites of contacts with DNA substrates on the surface of ASV IN.

Piecing together the structure of retroviral integrase, an important target in AIDS therapy.

Integrase (IN) is one of only three enzymes encoded in the genomes of all retroviruses, and is the one least characterized in structural terms. IN catalyzes processing of the ends of a DNA copy of the retroviral genome and its concerted insertion into the chromosome of the host cell. The protein consists of three domains, the central catalytic core domain flanked by the N-terminal and C-terminal domains, the latter being involved in DNA binding.

Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody.

The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-angstroms resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132.

Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics.

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate-biosynthetic pathway and is essential for microorganisms but absent from mammals. HPPK catalyzes Mg(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). Previously, three-dimensional structures of Escherichia coli HPPK (EcHPPK) have been determined at almost every stage of its catalytic cycle and the reaction mechanism has been established.

Interactions between HIV-1 Gag molecules in solution: an inositol phosphate-mediated switch.

Retrovirus particle assembly is mediated by the Gag protein. Gag is a multi-domain protein containing discrete domains connected by flexible linkers. When recombinant HIV-1 Gag protein (lacking myristate at its N terminus and the p6 domain at its C terminus) is mixed with nucleic acid, it assembles into virus-like particles (VLPs) in a fully defined system in vitro.

Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design.

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 through P5'. Although HTLV-1 PR exhibits an overall fold similar to other retroviral PRs, significant structural differences are present in several loop areas, which include the functionally important flaps, previously considered to be structurally highly conserved.

Integrase of Mason-Pfizer monkey virus.

The gene encoding an integrase of Mason-Pfizer monkey virus (M-PMV) is located at the 3'-end of the pol open reading frame. The M-PMV integrase has not been previously isolated and characterized. We have now cloned, expressed, isolated, and characterized M-PMV integrase and compared its activities and primary structure with those of HIV-1 and other retroviral integrases.

Total chemical synthesis of N-myristoylated HIV-1 matrix protein p17: structural and mechanistic implications of p17 myristoylation.

The HIV-1 matrix protein p17, excised proteolytically from the N terminus of the Gag polyprotein, forms a protective shell attached to the inner surface of the plasma membrane of the virus. During the late stages of the HIV-1 replication cycle, the N-terminally myristoylated p17 domain targets the Gag polyprotein to the host-cell membrane for particle assembly. In the early stages of HIV-1 replication, however, some p17 molecules dissociate from the viral membrane to direct the preintegration complex to the host-cell nucleus.