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Title
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X-ray analysis (1. 4-A resolution) of avian pancreatic polypeptide: Small globular protein hormone.
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Authors
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T.L.Blundell,
J.E.Pitts,
I.J.Tickle,
S.P.Wood,
C.W.Wu.
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Ref.
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Proc Natl Acad Sci U S A, 1981,
78,
4175-4179.
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PubMed id
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Abstract
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The crystal structure of avian pancreatic polypeptide (aPP), a 36-residue
polypeptide with some hormonal properties, has been determined by using single
isomorphous replacement and anomalous scattering to 2.1-A resolution. The phases
were extended to 1.4-A resolution by using a modified tangent formula. The
molecule contains two regions of secondary structure-an extended
polyproline-like helix (residues 1-8) and an alpha-helix (residues 14-31)-that
run roughly antiparallel. The packing together of nonpolar groups from these
regions gives the molecule a hydrophobic core in spite of its small size. The
aPP molecules form a symmetrical dimer in the crystal stabilized principally by
interlocking of nonpolar groups from the alpha-helices. The aPP dimers are
crosslinked by coordination of Zn(2+); three aPP molecules contribute ligands to
each zinc. The coordination geometry is a distorted trigonal bipyramid. The
properties of the aPP molecule in solution are consistent with expectations
based on the crystal structure. The aPP molecule has several general features in
common with the pancreatic hormones insulin and glucagon. All three hormones
have complex mechanisms for self-association. Like insulin, aPP seems to have a
stable monomeric structure but its biological activity seems to depend on the
more flexible COOH-terminal region analogous to the flexible NH(2)-terminal
region of glucagon.
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