CVN_NOSEL
ID CVN_NOSEL Reviewed; 101 AA.
AC P81180;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 25-MAY-2022, entry version 85.
DE RecName: Full=Cyanovirin-N;
DE Short=CV-N;
OS Nostoc ellipsosporum.
OC Bacteria; Cyanobacteria; Nostocales; Nostocaceae; Nostoc.
OX NCBI_TaxID=45916;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, STABILITY, BIOTECHNOLOGY (EXPRESSION IN
RP E.COLI), AND INTERACTION WITH HIV-1 GP120.
RX PubMed=9210678; DOI=10.1128/aac.41.7.1521;
RA Boyd M.R., Gustafson K.R., McMahon J.B., Shoemaker R.H., O'Keefe B.R.,
RA Mori T., Gulakowski R.J., Wu L., Rivera M.I., Laurencot C.M., Currens M.J.,
RA Cardellina J.H. II, Buckheit R.W. Jr., Nara P.L., Pannell L.K.,
RA Sowder R.C. II, Henderson L.E.;
RT "Discovery of cyanovirin-N, a novel human immunodeficiency virus-
RT inactivating protein that binds viral surface envelope glycoprotein gp120:
RT potential applications to microbicide development.";
RL Antimicrob. Agents Chemother. 41:1521-1530(1997).
RN [2]
RP PROTEIN SEQUENCE, MASS SPECTROMETRY, DISULFIDE BONDS, AND DISULFIDE BOND.
RX PubMed=9299483; DOI=10.1006/bbrc.1997.7203;
RA Gustafson K.R., Sowder R.C. II, Henderson L.E., Cardellina J.H. II,
RA McMahon J.B., Rajamani U., Pannell L.K., Boyd M.R.;
RT "Isolation, primary sequence determination, and disulfide bond structure of
RT cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the
RT cyanobacterium Nostoc ellipsosporum.";
RL Biochem. Biophys. Res. Commun. 238:223-228(1997).
RN [3]
RP VIRAL SUBSTRATES.
RX PubMed=10775592; DOI=10.1128/jvi.74.10.4562-4569.2000;
RA Dey B., Lerner D.L., Lusso P., Boyd M.R., Elder J.H., Berger E.A.;
RT "Multiple antiviral activities of cyanovirin-N: blocking of human
RT immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and
RT inhibition of diverse enveloped viruses.";
RL J. Virol. 74:4562-4569(2000).
RN [4]
RP BIOTECHNOLOGY (EXPRESSION IN PICHIA PASTORIS), AND MUTAGENESIS OF ASN-30.
RX PubMed=12356469; DOI=10.1016/s1046-5928(02)00513-2;
RA Mori T., Barrientos L.G., Han Z., Gronenborn A.M., Turpin J.A., Boyd M.R.;
RT "Functional homologs of cyanovirin-N amenable to mass production in
RT prokaryotic and eukaryotic hosts.";
RL Protein Expr. Purif. 26:42-49(2002).
RN [5]
RP FUNCTION.
RX PubMed=12678493; DOI=10.1007/s000180300023;
RA Botos I., Wlodawer A.;
RT "Cyanovirin-N: a sugar-binding antiviral protein with a new twist.";
RL Cell. Mol. Life Sci. 60:277-287(2003).
RN [6]
RP BIOTECHNOLOGY (EXPRESSION IN LACTOBACILLUS JENSENII).
RX PubMed=17005802; DOI=10.1128/aac.00493-06;
RA Liu X., Lagenaur L.A., Simpson D.A., Essenmacher K.P., Frazier-Parker C.L.,
RA Liu Y., Tsai D., Rao S.S., Hamer D.H., Parks T.P., Lee P.P., Xu Q.;
RT "Engineered vaginal lactobacillus strain for mucosal delivery of the human
RT immunodeficiency virus inhibitor cyanovirin-N.";
RL Antimicrob. Agents Chemother. 50:3250-3259(2006).
RN [7]
RP BIOTECHNOLOGY (EXPRESSION IN NICOTIANA TABACUM).
RX PubMed=16354721; DOI=10.1096/fj.05-4742fje;
RA Sexton A., Drake P.M., Mahmood N., Harman S.J., Shattock R.J., Ma J.K.;
RT "Transgenic plant production of Cyanovirin-N, an HIV microbicide.";
RL FASEB J. 20:356-358(2006).
RN [8]
RP BIOTECHNOLOGY (EXPRESSION IN ESCHERICHIA COLI).
RX PubMed=19547966; DOI=10.1007/s00253-009-2078-5;
RA Gao X., Chen W., Guo C., Qian C., Liu G., Ge F., Huang Y., Kitazato K.,
RA Wang Y., Xiong S.;
RT "Soluble cytoplasmic expression, rapid purification, and characterization
RT of cyanovirin-N as a His-SUMO fusion.";
RL Appl. Microbiol. Biotechnol. 85:1051-1060(2010).
RN [9]
RP REVIEW.
RX PubMed=20162270; DOI=10.1007/s00253-010-2470-1;
RA Xiong S., Fan J., Kitazato K.;
RT "The antiviral protein cyanovirin-N: the current state of its production
RT and applications.";
RL Appl. Microbiol. Biotechnol. 86:805-812(2010).
RN [10]
RP STRUCTURE BY NMR.
RX PubMed=9665171; DOI=10.1038/828;
RA Bewley C.A., Gustafson K.R., Boyd M.R., Covell D.G., Bax A., Clore G.M.,
RA Gronenborn A.M.;
RT "Solution structure of cyanovirin-N, a potent HIV-inactivating protein.";
RL Nat. Struct. Biol. 5:571-578(1998).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=10329150; DOI=10.1006/jmbi.1999.2693;
RA Yang F., Bewley C.A., Louis J.M., Gustafson K.R., Boyd M.R.,
RA Gronenborn A.M., Clore G.M., Wlodawer A.;
RT "Crystal structure of cyanovirin-N, a potent HIV-inactivating protein,
RT shows unexpected domain swapping.";
RL J. Mol. Biol. 288:403-412(1999).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH HIGH-MANNOSE
RP OLIGOSACCHARIDES.
RX PubMed=12110688; DOI=10.1074/jbc.m205909200;
RA Botos I., O'Keefe B.R., Shenoy S.R., Cartner L.K., Ratner D.M.,
RA Seeberger P.H., Boyd M.R., Wlodawer A.;
RT "Structures of the complexes of a potent anti-HIV protein cyanovirin-N and
RT high mannose oligosaccharides.";
RL J. Biol. Chem. 277:34336-34342(2002).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), STRUCTURE BY NMR, SUBUNIT, AND
RP MUTAGENESIS OF PRO-51 AND SER-52.
RX PubMed=12015150; DOI=10.1016/s0969-2126(02)00758-x;
RA Barrientos L.G., Louis J.M., Botos I., Mori T., Han Z., O'Keefe B.R.,
RA Boyd M.R., Wlodawer A., Gronenborn A.M.;
RT "The domain-swapped dimer of cyanovirin-N is in a metastable folded state:
RT reconciliation of X-ray and NMR structures.";
RL Structure 10:673-686(2002).
CC -!- FUNCTION: Mannose-binding lectin. {ECO:0000269|PubMed:12678493,
CC ECO:0000269|PubMed:9210678}.
CC -!- SUBUNIT: In solution exists as a metastable domain-swapped homodimer
CC which very slowly converts into a more stable monomeric form at room
CC temperature. Under physiological conditions it is unlikely that the
CC dimeric species exists and indeed the monomer is more active against
CC HIV. Interacts with HIV-1 gp120. {ECO:0000269|PubMed:12015150,
CC ECO:0000269|PubMed:12110688, ECO:0000269|PubMed:9210678}.
CC -!- PTM: Cleavage, or reduction and alkylation of the disulfide bonds
CC results in the loss of anti-HIV activity.
CC -!- MASS SPECTROMETRY: Mass=11014.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:9299483};
CC -!- BIOTECHNOLOGY: Overexpression of this protein to provide quantities
CC adequate for medical use as a topical microbiocide has been attempted
CC in a number of systems including E.coli (PubMed:9210678,
CC PubMed:19547966), Lactobacillus jensenii (PubMed:17005802), the yeast
CC Pichia pastoris (PubMed:12356469) and Nicotiana tabacum
CC (PubMed:16354721); see PubMed:20162270 for a review.
CC {ECO:0000269|PubMed:12356469, ECO:0000269|PubMed:16354721,
CC ECO:0000269|PubMed:17005802, ECO:0000269|PubMed:19547966,
CC ECO:0000269|PubMed:9210678}.
CC -!- MISCELLANEOUS: Its activity in situ is unknown, however it acts as a
CC viral entry inhibitor, inhibiting HIV-1, HIV-2 and simian
CC immunodeficiency virus (and some other viruses such as feline
CC immunodeficiency virus, measles virus and human herpesvirus) infection
CC and replication. It prevents essential interactions between the
CC envelope glycoprotein and target cell receptors by binding to
CC carbohydrates on viral protein gp120 and possibly by other mechanisms
CC as well. Addition to cells must occur before or shortly after virus
CC addition. It also inhibits cell-to-cell fusion, and virus-to-cell and
CC cell-to-cell transmission of a viral infection.
CC -!- MISCELLANEOUS: Is remarkably stabile; the protein can withstand
CC multiple freeze-thaw cycles, dissolution in organic solvents, treatment
CC with salt, detergent, H(2)O(2) and boiling without significant loss of
CC anti-HIV activity.
CC -!- SIMILARITY: Belongs to the cyanovirin-N family. {ECO:0000305}.
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DR PIR; JC5631; JC5631.
DR PDB; 1IIY; NMR; -; A=1-101.
DR PDB; 1J4V; NMR; -; A/B=1-101.
DR PDB; 1L5B; X-ray; 2.00 A; A/B=1-101.
DR PDB; 1L5E; NMR; -; A/B=1-101.
DR PDB; 1LOM; X-ray; 1.72 A; A=1-101.
DR PDB; 1N02; NMR; -; A=1-101.
DR PDB; 2EZM; NMR; -; A=1-101.
DR PDB; 2EZN; NMR; -; A=1-101.
DR PDB; 2PYS; X-ray; 1.80 A; A/B=1-101.
DR PDB; 2RDK; X-ray; 1.35 A; A/B=1-101.
DR PDB; 2RP3; NMR; -; A=1-101.
DR PDB; 2Z21; X-ray; 1.80 A; A/B=1-101.
DR PDB; 3CZZ; X-ray; 1.36 A; A/B=1-101.
DR PDB; 3EZM; X-ray; 1.50 A; A=1-101.
DR PDB; 3GXY; X-ray; 2.40 A; A/B=1-101.
DR PDB; 3GXZ; X-ray; 2.50 A; A/B=1-101.
DR PDB; 3LHC; X-ray; 1.34 A; A=1-101.
DR PDB; 3S3Y; X-ray; 2.00 A; A=1-101.
DR PDB; 3S3Z; X-ray; 1.75 A; A=1-101.
DR PDB; 4J4C; X-ray; 1.90 A; A=1-101.
DR PDB; 4J4D; X-ray; 2.00 A; A/B/C/D=1-101.
DR PDB; 4J4E; X-ray; 2.40 A; A/B/C/D/E/F=1-101.
DR PDB; 4J4F; X-ray; 1.90 A; A/B/C/D=1-101.
DR PDB; 4J4G; X-ray; 1.92 A; A/B/C/D=1-101.
DR PDB; 6X7H; X-ray; 1.25 A; A/B=1-101.
DR PDBsum; 1IIY; -.
DR PDBsum; 1J4V; -.
DR PDBsum; 1L5B; -.
DR PDBsum; 1L5E; -.
DR PDBsum; 1LOM; -.
DR PDBsum; 1N02; -.
DR PDBsum; 2EZM; -.
DR PDBsum; 2EZN; -.
DR PDBsum; 2PYS; -.
DR PDBsum; 2RDK; -.
DR PDBsum; 2RP3; -.
DR PDBsum; 2Z21; -.
DR PDBsum; 3CZZ; -.
DR PDBsum; 3EZM; -.
DR PDBsum; 3GXY; -.
DR PDBsum; 3GXZ; -.
DR PDBsum; 3LHC; -.
DR PDBsum; 3S3Y; -.
DR PDBsum; 3S3Z; -.
DR PDBsum; 4J4C; -.
DR PDBsum; 4J4D; -.
DR PDBsum; 4J4E; -.
DR PDBsum; 4J4F; -.
DR PDBsum; 4J4G; -.
DR PDBsum; 6X7H; -.
DR AlphaFoldDB; P81180; -.
DR SMR; P81180; -.
DR DrugBank; DB03309; N-cyclohexyltaurine.
DR DrugBank; DB02695; O1-Pentyl-Mannose.
DR UniLectin; P81180; -.
DR EvolutionaryTrace; P81180; -.
DR GO; GO:0030246; F:carbohydrate binding; IDA:UniProtKB.
DR GO; GO:0050688; P:regulation of defense response to virus; IDA:UniProtKB.
DR Gene3D; 2.30.60.10; -; 1.
DR InterPro; IPR011058; Cyanovirin-N.
DR InterPro; IPR036673; Cyanovirin-N_sf.
DR Pfam; PF08881; CVNH; 1.
DR SMART; SM01111; CVNH; 1.
DR SUPFAM; SSF51322; SSF51322; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral protein; Direct protein sequencing; Disulfide bond;
KW Lectin.
FT CHAIN 1..101
FT /note="Cyanovirin-N"
FT /id="PRO_0000079579"
FT DISULFID 8..22
FT /evidence="ECO:0000269|PubMed:9299483"
FT DISULFID 58..73
FT /evidence="ECO:0000269|PubMed:9299483"
FT MUTAGEN 30
FT /note="N->A,Q,V: Prevents N-glycosylation upon
FT overexpression in yeast without changing anti-HIV
FT activity."
FT /evidence="ECO:0000269|PubMed:12356469"
FT MUTAGEN 51
FT /note="P->G: Protein is mostly monomeric and has wild-type
FT anti-HIV activity."
FT /evidence="ECO:0000269|PubMed:12015150"
FT MUTAGEN 52
FT /note="S->P: Protein is exclusively dimeric and has
FT moderate anti-HIV activity."
FT /evidence="ECO:0000269|PubMed:12015150"
FT HELIX 4..6
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 17..23
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:1L5B"
FT STRAND 29..35
FT /evidence="ECO:0007829|PDB:6X7H"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:6X7H"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:6X7H"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:3GXZ"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:6X7H"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:6X7H"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:6X7H"
SQ SEQUENCE 101 AA; 11013 MW; 1F8FA5B88ACCE57F CRC64;
LGKFSQTCYN SAIQGSVLTS TCERTNGGYN TSSIDLNSVI ENVDGSLKWQ PSNFIETCRN
TQLAGSSELA AECKTRAQQF VSTKINLDDH IANIDGTLKY E
