Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides Export

@article{citeulike:841049, abstract = {The development of anti-human immunodeficiency virus (HIV) microbicides for either topical or ex vivo use is of considerable interest, mainly due to the difficulties in creating a vaccine that would be active against multiple clades of HIV. Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium (blue-green algae) Nostoc ellipsosporum with potent virucidal activity, was identified in the search for such antiviral agents. The binding of CV-N to the heavily glycosylated HIV envelope protein gp120 is carbohydrate-dependent. Since previous CV-N-dimannose structures could not fully explain CV-N-oligomannose binding, we determined the crystal structures of recombinant CV-N complexed to Man-9 and a synthetic hexamannoside, at 2.5- and 2.4-A resolution, respectively. CV-N is a three-dimensional domain-swapped dimer in the crystal structures with two primary sites near the hinge region and two secondary sites on the opposite ends of the dimer. The binding interface is constituted of three stacked [alpha]1[right-arrow]2-linked mannose rings for Man-9 and two stacked mannose rings for hexamannoside with the rest of the saccharide molecules pointing to the solution. These structures show unequivocally the binding geometry of high mannose sugars to CV-N, permitting a better understanding of carbohydrate binding to this potential new lead for the design of drugs against AIDS. 10.1074/jbc.M205909200}, author = {Botos, Istvan and O'Keefe, Barry R. and Shenoy, Shilpa R. and Cartner, Laura K. and Ratner, Daniel M. and Seeberger, Peter H. and Boyd, Michael R. and Wlodawer, Alexander}, citeulike-article-id = {841049}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M205909200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/277/37/34336}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12110688}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12110688}, day = {6}, doi = {10.1074/jbc.M205909200}, journal = {J. Biol. Chem.}, keywords = {dimer, domain\_swapping, protein, structure, xray-crystal-structure}, month = {September}, number = {37}, pages = {34336--34342}, posted-at = {2009-01-27 07:47:15}, priority = {2}, title = {Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides}, url = {http://dx.doi.org/10.1074/jbc.M205909200}, volume = {277}, year = {2002} }

TY - JOUR ID - citeulike:841049 L3 - citeulike-article-id:841049 N2 - The development of anti-human immunodeficiency virus (HIV) microbicides for either topical or ex vivo use is of considerable interest, mainly due to the difficulties in creating a vaccine that would be active against multiple clades of HIV. Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium (blue-green algae) Nostoc ellipsosporum with potent virucidal activity, was identified in the search for such antiviral agents. The binding of CV-N to the heavily glycosylated HIV envelope protein gp120 is carbohydrate-dependent. Since previous CV-N-dimannose structures could not fully explain CV-N-oligomannose binding, we determined the crystal structures of recombinant CV-N complexed to Man-9 and a synthetic hexamannoside, at 2.5- and 2.4-A resolution, respectively. CV-N is a three-dimensional domain-swapped dimer in the crystal structures with two primary sites near the hinge region and two secondary sites on the opposite ends of the dimer. The binding interface is constituted of three stacked [alpha]1[right-arrow]2-linked mannose rings for Man-9 and two stacked mannose rings for hexamannoside with the rest of the saccharide molecules pointing to the solution. These structures show unequivocally the binding geometry of high mannose sugars to CV-N, permitting a better understanding of carbohydrate binding to this potential new lead for the design of drugs against AIDS. 10.1074/jbc.M205909200 IS - 37 JF - J. Biol. Chem. EP - 34342 TI - Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides VL - 277 SP - 34336 KW - dimer KW - domain_swapping KW - protein KW - structure KW - xray-crystal-structure AU - Botos, Istvan AU - O'Keefe, Barry AU - Shenoy, Shilpa AU - Cartner, Laura AU - Ratner, Daniel AU - Seeberger, Peter AU - Boyd, Michael AU - Wlodawer, Alexander PY - 2002/09/06/ UR - http://dx.doi.org/10.1074/jbc.M205909200 ER -