title: Azurin, Plasmodium falciparum malaria and HIV/AIDS: inhibition of parasitic and viral growth by Azurin.
abstract: Azurin, a member of a family of copper-containing proteins involved in electron transfer called cupredoxins, demonstrates structural features similar to the variable domains of the immunoglobulin superfamily members. An azurin-like protein called Laz with an additional N-terminal 39 amino acid peptide known as H.8 epitope is present on the surface of gonnococci and meningococci. We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia. Azurin and Laz also bound strongly to HIV-1 gp120. Interestingly, azurin could not only bind to gp120 but also to the dendritic cell-specific adhesion receptor DC-SIGN, mimicking the functionality of the intercellular adhesion molecule ICAM-3 with which it also binds avidly. Furthermore, these three proteins significantly suppressed HIV-1 growth in peripheral blood mononuclear cells and such suppression appeared to be occurring at an entry stage in the infection process. The presence of both antimalarial and antiretroviral activity in azurin, H.8-azurin and Laz makes these proteins, or peptides derived from them, potential therapeutic agents in the treatment of malaria, HIV-1 infections or coinfections with both P. falciparum and HIV-1.
authors.affiliation: Department of Microbiology & Immunology, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Chaudhari
authors.forename: Arsenio M
authors.initials: AM
authors.lastname: Fialho
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Hong
authors.forename: Soumen
authors.initials: S
authors.lastname: Kahali
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamada
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
authors.forename: Sean
authors.initials: S
authors.lastname: Murphy
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Cho
authors.forename: Virander S
authors.initials: VS
authors.lastname: Chauhan
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Das Gupta
authors.forename: Ananda M
authors.initials: AM
authors.lastname: Chakrabarty
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001400:Azurin / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development* / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D016778:Malaria, Falciparum / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D009343:Neisseria / Q000737:chemistry / Q000276:immunology; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000502:physiology*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000942:Antigens, Bacterial; D001400:Azurin; D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D037181:Lectins, C-Type; D020066:Merozoite Surface Protein 1; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C055700:H.8 protein (Neisseria)