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PDB id:
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Hormone
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Title:
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[D-alab26]-des(b27-b30)-insulin-b26-amide a superpotent single-replacement insulin analogue, nmr, minimized average structure
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Structure:
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Insulin. Chain: a. Engineered: yes. Mutation: yes. Insulin. Chain: b. Engineered: yes. Mutation: yes
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Source:
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Synthetic construct. Organism_taxid: 32630
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NMR struc:
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1 models
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Authors:
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G.Kurapkat,M.Siedentopf,H.G.Gattner,M.Hagelstein, D.Brandenburg,J.Grotzinger,A.Wollmer
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Key ref:
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G.Kurapkat
et al.
(1999).
The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue.
Protein Sci,
8,
499-508.
PubMed id:
Ref:
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Date:
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04-Nov-98
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Release date:
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18-May-99
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PROCHECK
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Headers
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References
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biochemical function
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hormone activity
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1 term
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Protein Sci
8:499-508
(1999)
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PubMed id:
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The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue.
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G.Kurapkat,
M.Siedentop,
H.G.Gattner,
M.Hagelstein,
D.Brandenburg,
J.Grötzinger,
A.Wollmer.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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Google scholar
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PubMed id
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Reference
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J.Jirácek,
L.Záková,
E.Antolíková,
C.J.Watson,
J.P.Turkenburg,
G.G.Dodson,
and
A.M.Brzozowski
(2010).
Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues.
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Proc Natl Acad Sci U S A, 107,
1966-1970.
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B.Xu,
K.Huang,
Y.C.Chu,
S.Q.Hu,
S.Nakagawa,
S.Wang,
R.Y.Wang,
J.Whittaker,
P.G.Katsoyannis,
and
M.A.Weiss
(2009).
Decoding the Cryptic Active Conformation of a Protein by Synthetic Photoscanning: INSULIN INSERTS A DETACHABLE ARM BETWEEN RECEPTOR DOMAINS.
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J Biol Chem, 284,
14597-14608.
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Q.X.Hua,
B.Xu,
K.Huang,
S.Q.Hu,
S.Nakagawa,
W.Jia,
S.Wang,
J.Whittaker,
P.G.Katsoyannis,
and
M.A.Weiss
(2009).
Enhancing the Activity of a Protein by Stereospecific Unfolding: CONFORMATIONAL LIFE CYCLE OF INSULIN AND ITS EVOLUTIONARY ORIGINS.
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J Biol Chem, 284,
14586-14596.
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PDB codes:
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J.P.Mayer,
F.Zhang,
and
R.D.DiMarchi
(2007).
Insulin structure and function.
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Biopolymers, 88,
687-713.
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J.B.Mitchell,
and
J.Smith
(2003).
D-amino acid residues in peptides and proteins.
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Proteins, 50,
563-571.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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