1apf: Difference between revisions

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[[Image:1apf.gif|left|200px]]<br /><applet load="1apf" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1apf.gif|left|200px]]<br /><applet load="1apf" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1apf" />

'''ANTHOPLEURIN-B, NMR, 20 STRUCTURES'''<br />

==Overview==

BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of, related toxins produced by sea anemones. AP-B delays inactivation of the, voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a, result, there is interest in exploiting the anthopleurins as lead, compounds in the design of novel cardiac stimulants. Essential to this, endeavour is a high-resolution solution structure of the molecule, describing the positions of functionally important side chains. RESULTS:, AP-B exists in multiple conformations in solution as a result of cis-trans, isomerization about the Gly40-Pro41 peptide bond. The solution structure, of the major conformer of AP-B has been determined by two-dimensional 1H, NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded, antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and, includes several beta-turns (6-9, 25-28, 30-33). Three loops connect the, beta-strands, the longest and least well defined being the first loop, extending from residues 8-17. These features are shared by other members, of this family of sea anemone toxins. The locations of a number of side, chains which are important for the cardiac stimulatory activity of AP-B, are well defined in the structures. CONCLUSIONS: We have described the, solution structure of AP-B and compared it with that of AP-A, from which, it differs by substitutions at seven amino acid positions. It shares an, essentially identical fold with AP-A yet is about 10-fold more active., Comparison of the structures, particularly in the region of residues, essential for activity, gives a clearer indication of the location and, extent of the cardioactive pharmacophore in these polypeptides.

BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of related toxins produced by sea anemones. AP-B delays inactivation of the voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a result, there is interest in exploiting the anthopleurins as lead compounds in the design of novel cardiac stimulants. Essential to this endeavour is a high-resolution solution structure of the molecule describing the positions of functionally important side chains. RESULTS: AP-B exists in multiple conformations in solution as a result of cis-trans isomerization about the Gly40-Pro41 peptide bond. The solution structure of the major conformer of AP-B has been determined by two-dimensional 1H NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded, antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and includes several beta-turns (6-9, 25-28, 30-33). Three loops connect the beta-strands, the longest and least well defined being the first loop, extending from residues 8-17. These features are shared by other members of this family of sea anemone toxins. The locations of a number of side chains which are important for the cardiac stimulatory activity of AP-B are well defined in the structures. CONCLUSIONS: We have described the solution structure of AP-B and compared it with that of AP-A, from which it differs by substitutions at seven amino acid positions. It shares an essentially identical fold with AP-A yet is about 10-fold more active. Comparison of the structures, particularly in the region of residues essential for activity, gives a clearer indication of the location and extent of the cardioactive pharmacophore in these polypeptides.

==About this Structure==

1APF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Anthopleura_xanthogrammica Anthopleura xanthogrammica]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1APF OCA].

1APF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Anthopleura_xanthogrammica Anthopleura xanthogrammica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1APF OCA].

==Reference==

Line 13:

[[Category: Anthopleura xanthogrammica]]

[[Category: Single protein]]

[[Category: Monks, S.A.]]

[[Category: Monks, S A.]]

[[Category: Norton, R.S.]]

[[Category: Norton, R S.]]

[[Category: Pallaghy, P.K.]]

[[Category: Pallaghy, P K.]]

[[Category: Scanlon, M.J.]]

[[Category: Scanlon, M J.]]

[[Category: cardiac stimulant]]

[[Category: sea anemone]]

[[Category: toxin]]

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@@ Line 1: / Line 1: @@
-[[Image:1apf.gif|left|200px]]<br /><applet load="1apf" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1apf.gif|left|200px]]<br /><applet load="1apf" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1apf" />
 '''ANTHOPLEURIN-B, NMR, 20 STRUCTURES'''<br />
 ==Overview==
-BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of, related toxins produced by sea anemones. AP-B delays inactivation of the, voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a, result, there is interest in exploiting the anthopleurins as lead, compounds in the design of novel cardiac stimulants. Essential to this, endeavour is a high-resolution solution structure of the molecule, describing the positions of functionally important side chains. RESULTS:, AP-B exists in multiple conformations in solution as a result of cis-trans, isomerization about the Gly40-Pro41 peptide bond. The solution structure, of the major conformer of AP-B has been determined by two-dimensional 1H, NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded, antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and, includes several beta-turns (6-9, 25-28, 30-33). Three loops connect the, beta-strands, the longest and least well defined being the first loop, extending from residues 8-17. These features are shared by other members, of this family of sea anemone toxins. The locations of a number of side, chains which are important for the cardiac stimulatory activity of AP-B, are well defined in the structures. CONCLUSIONS: We have described the, solution structure of AP-B and compared it with that of AP-A, from which, it differs by substitutions at seven amino acid positions. It shares an, essentially identical fold with AP-A yet is about 10-fold more active., Comparison of the structures, particularly in the region of residues, essential for activity, gives a clearer indication of the location and, extent of the cardioactive pharmacophore in these polypeptides.
+BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of related toxins produced by sea anemones. AP-B delays inactivation of the voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a result, there is interest in exploiting the anthopleurins as lead compounds in the design of novel cardiac stimulants. Essential to this endeavour is a high-resolution solution structure of the molecule describing the positions of functionally important side chains. RESULTS: AP-B exists in multiple conformations in solution as a result of cis-trans isomerization about the Gly40-Pro41 peptide bond. The solution structure of the major conformer of AP-B has been determined by two-dimensional 1H NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded, antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and includes several beta-turns (6-9, 25-28, 30-33). Three loops connect the beta-strands, the longest and least well defined being the first loop, extending from residues 8-17. These features are shared by other members of this family of sea anemone toxins. The locations of a number of side chains which are important for the cardiac stimulatory activity of AP-B are well defined in the structures. CONCLUSIONS: We have described the solution structure of AP-B and compared it with that of AP-A, from which it differs by substitutions at seven amino acid positions. It shares an essentially identical fold with AP-A yet is about 10-fold more active. Comparison of the structures, particularly in the region of residues essential for activity, gives a clearer indication of the location and extent of the cardioactive pharmacophore in these polypeptides.
 ==About this Structure==
-APF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Anthopleura_xanthogrammica Anthopleura xanthogrammica]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1APF OCA].
+APF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Anthopleura_xanthogrammica Anthopleura xanthogrammica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1APF OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Anthopleura xanthogrammica]]
 [[Category: Single protein]]
-[[Category: Monks, S.A.]]
+[[Category: Monks, S A.]]
-[[Category: Norton, R.S.]]
+[[Category: Norton, R S.]]
-[[Category: Pallaghy, P.K.]]
+[[Category: Pallaghy, P K.]]
-[[Category: Scanlon, M.J.]]
+[[Category: Scanlon, M J.]]
 [[Category: cardiac stimulant]]
 [[Category: sea anemone]]
 [[Category: toxin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 11:01:23 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:46:55 2008''