|
|
| Line 1: |
Line 1: |
| [[Image:1ryv.jpg|left|200px]] | | {{Seed}} |
| | [[Image:1ryv.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1ryv| PDB=1ryv | SCENE= }} | | {{STRUCTURE_1ryv| PDB=1ryv | SCENE= }} |
|
| |
|
| '''Three dimensional solution structure of the K27A MUTANT of sodium channels inhibitor HAINANTOXIN-IV BY 2D 1H-NMR'''
| | ===Three dimensional solution structure of the K27A MUTANT of sodium channels inhibitor HAINANTOXIN-IV BY 2D 1H-NMR=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15201273}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15201273 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15201273}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| 1RYV is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYV OCA]. | | 1RYV is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYV OCA]. |
|
| |
|
| ==Reference== | | ==Reference== |
| Line 27: |
Line 31: |
| [[Category: Inhibitor cystine knot motif]] | | [[Category: Inhibitor cystine knot motif]] |
| [[Category: Neurotoxin]] | | [[Category: Neurotoxin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:04:53 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:14:37 2008'' |
