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1bzv

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Revision as of 09:28, 10 September 2015

[D-ALAB26]-DES(B27-B30)-INSULIN-B26-AMIDE A SUPERPOTENT SINGLE-REPLACEMENT INSULIN ANALOGUE, NMR, MINIMIZED AVERAGE STRUCTURE

Structural highlights

1bzv is a 2 chain structure with sequence from Synthetic construct sequences. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[INS_BALPH] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. [INS_PANTR] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

Publication Abstract from PubMed

This paper reports on an insulin analogue with 12.5-fold receptor affinity, the highest increase observed for a single replacement, and on its solution structure, determined by NMR spectroscopy. The analogue is [D-AlaB26]des-(B27-B30)-tetrapeptide-insulin-B26-amide. C-terminal truncation of the B-chain by four (or five) residues is known not to affect the functional properties of insulin, provided the new carboxylate charge is neutralized. As opposed to the dramatic increase in receptor affinity caused by the substitution of D-Ala for the wild-type residue TyrB26 in the truncated molecule, this very substitution reduces it to only 18% of that of the wild-type hormone when the B-chain is present in full length. The insulin molecule in solution is visualized as an ensemble of conformers interrelated by a dynamic equilibrium. The question is whether the "active" conformation of the hormone, sought after in innumerable structure/function studies, is or is not included in the accessible conformational space, so that it could be adopted also in the absence of the receptor. If there were any chance for the active conformation, or at least a predisposed state to be populated to a detectable extent, this chance should be best in the case of a superpotent analogue. This was the motivation for the determination of the three-dimensional structure of [D-AlaB26]des-(B27-B30)-tetrapeptide-insulin-B26-amide. However, neither the NMR data nor CD spectroscopic comparison of a number of related analogues provided a clue concerning structural features predisposing insulin to high receptor affinity. After the present study it seems more likely than before that insulin will adopt its active conformation only when exposed to the force field of the receptor surface.

The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue.,Kurapkat G, Siedentop M, Gattner HG, Hagelstein M, Brandenburg D, Grotzinger J, Wollmer A Protein Sci. 1999 Mar;8(3):499-508. PMID:10091652^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kurapkat G, Siedentop M, Gattner HG, Hagelstein M, Brandenburg D, Grotzinger J, Wollmer A. The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue. Protein Sci. 1999 Mar;8(3):499-508. PMID:10091652

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bzv"

@@ Line 2: / Line 2: @@
 <StructureSection load='1bzv' size='340' side='right' caption='[[1bzv]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bzv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BZV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bzv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BZV FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bzv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bzv RCSB], [http://www.ebi.ac.uk/pdbsum/1bzv PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bzv OCA], [http://pdbe.org/1bzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bzv RCSB], [http://www.ebi.ac.uk/pdbsum/1bzv PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1bzv" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Synthetic construct]]
+[[Category: Synthetic construct sequences]]
 [[Category: Brandenburg, D]]
 [[Category: Gattner, H G]]

1bzv

From Proteopedia

Revision as of 09:28, 10 September 2015

[D-ALAB26]-DES(B27-B30)-INSULIN-B26-AMIDE A SUPERPOTENT SINGLE-REPLACEMENT INSULIN ANALOGUE, NMR, MINIMIZED AVERAGE STRUCTURE

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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