KIIIA (P02587) Protein Card

General Information
Name KIIIA
Alternative name(s) K3a,KIIIA-P1
Organism Conus kinoshitai
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor KIIIA precursor (1694)
Notes Block tetrodotoxin resistant (TTX-R) Na channels and the blockade is slow and reversible (Bulaj et al 2005). 10 μM rapidly blocks A-fiber compound action potentials in mouse sciatic nerve. Also blocks C-fiber CAPs [Wilson,M.J., Zhang,M (2015)]. Predominant disulfide isomer: [C1-C15,C2-C9,C4-C16]

Classification
Conopeptide class conotoxin
Gene superfamily M superfamily
Cysteine framework III
Pharmacological family mu conotoxin

Sequence
CCNCSSKWCRDHSRCC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 1884.13
Monoisotopic Mass 1882.63
Isoelectric Point 11.73
Extinction Coefficient [280nm] 5500.00

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50nhillRef
Nav1.2R. norvegicus5nMMcArthur,J.R. et al. (2011)
61nM+/-51.02Van Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)
Nav1.3R. norvegicus8uM+/-1Zhang,M.M. et al. (2007)
3.6uM+/-0.31.44Van Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)
Nav1.4R. norvegicus90nM+/-17Zhang,M.M. et al. (2007)
54nMMcArthur,J.R. et al. (2011)
48nM+/-61.26Van Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)
Nav1.5H. sapiens>10uMVan Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)
R. norvegicus287uM+/-40Zhang,M.M. et al. (2007)
Nav1.6M. musculus183nM+/-311.09Van Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)
240nM+/-30Wilson,M.J. et al. (2011)
Nav1.7R. norvegicus147nMMcArthur,J.R. et al. (2011)
Nav1.8H. sapiens>10uMVan Der Haegen,A. and Peigneur,S. and Tytgat,J. (2011)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus290nM+/-110Zhang,M.M. et al. (2007)
Nav1.2R. norvegicus5nM+/-5Wilson,M.J. et al. (2011)
0.005 uM+/-0.005Khoo,K.K. et al. (2009)
3nMZhang,M.M. et al. (2007)
5nMMcArthur,J.R. et al. (2011)
Nav1.3R. norvegicus4.6uMZhang,M.M. et al. (2007)
Nav1.4R. norvegicus50nMZhang,M.M. et al. (2007)
37nMMcArthur,J.R. et al. (2011)
Nav1.7R. norvegicus290nM+/-90Zhang,M.M. et al. (2007)
292nM+/-52Zhang,M.M. et al. (2013)
(+Navβ2)1.38uM+/-0.03Zhang,M.M. et al. (2013)
97nMMcArthur,J.R. et al. (2011)
(+Navβ4)930nM+/-240Zhang,M.M. et al. (2013)
(+Navβ3)420nM+/-60Zhang,M.M. et al. (2013)
(+Navβ1)244nM+/-25Zhang,M.M. et al. (2013)

Percentage inhibition: Voltage-Gated Sodium Channels

TargetOrganism% inhibitionConcentrationRef
Nav1.2R. norvegicus90+/-31uMZhang,M.M. et al. (2007)
Nav1.4R. norvegicus86+/-61uMZhang,M.M. et al. (2007)
Nav TTX-RR. pipiens96+/-25uMZhang,M.M. et al. (2006)

Synthetic variants
KIIA [W8dTrp]CCNCSSKwCRDHSRCC(nh2)
KIIIA [D11A]CCNCSSKWCRAHSRCC(nh2)
KIIIA [H12A]CCNCSSKWCRDASRCC(nh2)
KIIIA [K7A]CCNCSSAWCRDHSRCC(nh2)
KIIIA [K7NLeu]CCNCSS(Nle)WCRDHSRCC(nh2)
KIIIA [N3A]CCACSSKWCRDHSRCC(nh2)
KIIIA [R10A]CCNCSSKWCADHSRCC(nh2)
KIIIA [R14A]CCNCSSKWCRDHSACC(nh2)
KIIIA [S13A]CCNCSSKWCRDHARCC(nh2)
KIIIA [S5A]CCNCASKWCRDHSRCC(nh2)
KIIIA [S6A]CCNCSAKWCRDHSRCC(nh2)
KIIIA [W8A]CCNCSSKACRDHSRCC(nh2)
KIIIA [W8E]CCNCSSKECRDHSRCC(nh2)
KIIIA [W8L]CCNCSSKLCRDHSRCC(nh2)
KIIIA [W8Q]CCNCSSKQCRDHSRCC(nh2)
KIIIA [W8R]CCNCSSKRCRDHSRCC(nh2)
KIIIA-P2CCNCSSKWCRDHSRCC(nh2)
KIIIA[C1A,C9A]ACNCSSKWARDHSRCC(nh2)
KIIIA[C2A,C15A]CANCSSKWCRDHSRAC(nh2)
KIIIA[C4A,C16A]CCNASSKWCRDHSRCA(nh2)
KIIIA[Del1,S3/S4Aop,C9A]CNC(Aop)KWARDHARCC(nh2)

References
Bulaj,G., West,P.J., Garrett,J.E., Watkins,M., Zhang,M.M., Norton,R.S., Smith,B.J., Yoshikami,D. and Olivera,B.M. (2005) Novel conotoxins from Conus striatus and Conus kinoshitai selectively block TTX-resistant sodium channels Biochemistry 44:7259-7265
Khoo,K.K., Feng,Z.P., Smith,B.J., Zhang,M.M., Yoshikami,D., Olivera,B.M., Bulaj,G. and Norton,R.S. (2009) Structure of the Analgesic mu-Conotoxin KIIIA and Effects on the Structure and Function of Disulfide Deletion. Biochemistry 6:1210-1219
Zhang,M.M., Green,B.R., Catlin,P., Fiedler,B., Azam,L., Chadwick,A., Terlau,H., McArthur,J.R., French,R.J., Gulyas,J., Rivier,J.E., Smith,B.J., Norton,R.S., Olivera,B.M., Yoshikami,D. and Bulaj,G. (2007) Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J. Biol. Chem. 282:30699-30706
McArthur,J.R., Singh,G., McMaster,D., Winkfein,R., Tieleman,D.P. and French,R.J. (2011) Interactions of key charged residues contributing to selective block of neuronal sodium channels by μ-conotoxin KIIIA. Mol. Pharmacol. 80:573-584
Van Der Haegen,A., Peigneur,S. and Tytgat,J. (2011) Importance of position 8 in μ-conotoxin KIIIA for voltage-gated sodium channel selectivity. FEBS J. 278:3408-3418
Zhang,M.M., Wilson,M.J., Azam,L., Gajewiak,J., Rivier,J.E., Bulaj,G., Olivera,B.M. and Yoshikami,D. (2013) Co-expression of Na(V)β subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking μ-conotoxins. Br. J. Pharmacol. 168:1597-1610
Wilson,M.J., Zhang,M.M., Gajewiak,J., Azam,L., Rivier,J.E., Olivera,B.M. and Yoshikami,D. (2015) Α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ. J. Neurophysiol. 113:2289-2301

Internal links
Protein Precursor KIIIA precursor (1694)
Nucleic acids
Structure NMR solution structure of an analgesic Mu-contoxin KIIIA
NMR solution structure of Mu-conotoxin KIIIA

External links
Ncbi 2LXG_A

Tools