1m5m
From Proteopedia
(New page: 200px<br /> <applet load="1m5m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m5m, resolution 2.50Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1m5m.gif|left|200px]]<br /> | + | [[Image:1m5m.gif|left|200px]]<br /><applet load="1m5m" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1m5m" size=" | + | |
caption="1m5m, resolution 2.50Å" /> | caption="1m5m, resolution 2.50Å" /> | ||
'''CRYSTAL STRUCTURE OF CYANOVIRIN-N COMPLEXED TO OLIGOMANNOSE-9 (MAN-9)'''<br /> | '''CRYSTAL STRUCTURE OF CYANOVIRIN-N COMPLEXED TO OLIGOMANNOSE-9 (MAN-9)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The development of anti-human immunodeficiency virus (HIV) microbicides | + | 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 alpha1-->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. |
==About this Structure== | ==About this Structure== | ||
| - | 1M5M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Nostoc_ellipsosporum Nostoc ellipsosporum] with NHE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1M5M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Nostoc_ellipsosporum Nostoc ellipsosporum] with <scene name='pdbligand=NHE:'>NHE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Botos, I.]] | [[Category: Botos, I.]] | ||
| - | [[Category: Boyd, M | + | [[Category: Boyd, M R.]] |
| - | [[Category: Cartner, L | + | [[Category: Cartner, L K.]] |
| - | [[Category: Keefe, B | + | [[Category: Keefe, B R.O.]] |
| - | [[Category: Ratner, D | + | [[Category: Ratner, D M.]] |
| - | [[Category: Seeberger, P | + | [[Category: Seeberger, P H.]] |
| - | [[Category: Shenoy, S | + | [[Category: Shenoy, S R.]] |
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
[[Category: NHE]] | [[Category: NHE]] | ||
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[[Category: oligosaccharide]] | [[Category: oligosaccharide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:48 2008'' |
Revision as of 11:51, 21 February 2008
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CRYSTAL STRUCTURE OF CYANOVIRIN-N COMPLEXED TO OLIGOMANNOSE-9 (MAN-9)
Overview
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 alpha1-->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.
About this Structure
1M5M is a Single protein structure of sequence from Nostoc ellipsosporum with as ligand. Full crystallographic information is available from OCA.
Reference
Structures of the complexes of a potent anti-HIV protein cyanovirin-N and high mannose oligosaccharides., Botos I, O'Keefe BR, Shenoy SR, Cartner LK, Ratner DM, Seeberger PH, Boyd MR, Wlodawer A, J Biol Chem. 2002 Sep 13;277(37):34336-42. Epub 2002 Jul 10. PMID:12110688
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