title: Structure and Glycan Binding of a New Cyanovirin-N Homolog.
abstract: The HIV-1 envelope glycoprotein gp120 is heavily glycosylated and bears numerous high mannose sugars. These sugars can serve as targets for HIV-inactivating compounds, such as antibodies and lectins, which bind to the glycans and interfere with viral entry into the target cell. We determined the 1.6 Å x-ray structure of Cyt-CVNH, a recently identified lectin from the cyanobacterium Cyanothece(7424), and elucidated its glycan specificity by NMR. The Cyt-CVNH structure and glycan recognition profile are similar to those of other CVNH proteins, with each domain specifically binding to Manα(1-2)Manα units on the D1 and D3 arms of high mannose glycans. However, in contrast to CV-N, no cross-linking and precipitation of the cross-linked species in solution was observed upon Man-9 binding, allowing, for the first time, investigation of the interaction of Man-9 with a member of the CVNH family by NMR. HIV assays showed that Cyt-CVNH is able to inhibit HIV-1 with ∼4-fold higher potency than CV-N(P51G), a stabilized version of wild type CV-N. Therefore, Cyt-CVNH may qualify as a valuable lectin for potential microbicidal use.
authors.affiliation: From the Department of Structural Biology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15260.
authors.forename: Elena
authors.initials: E
authors.lastname: Matei
authors.affiliation: From the Department of Structural Biology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15260, the Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Rohan
authors.initials: R
authors.lastname: Basu
authors.affiliation: the Department of Pharmacology & Chemical Biology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, Biocrystallography Laboratory, Veterans Affairs Medical Center, Pittsburgh, Pennsylvania 15240.
authors.forename: William
authors.initials: W
authors.lastname: Furey
authors.affiliation: the Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, and.
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.affiliation: From the Department of Structural Biology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15260, the Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Conor
authors.initials: C
authors.lastname: Calnan
authors.affiliation: the Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.affiliation: From the Department of Structural Biology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15260, amg100@pitt.edu.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D002460:Cell Line; D018360:Crystallography, X-Ray; D046889:Cyanothece / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D037241:Mannose-Binding Lectins; C514793:gp120 protein, Human immunodeficiency virus 1; C107733:cyanovirin N; D008358:Mannose
keywords: X-ray crystallography; antiviral agent; human immunodeficiency virus (HIV); lectin; nuclear magnetic resonance (NMR); oligosaccharide