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Title
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Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function.
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Authors
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H.Loebermann,
R.Tokuoka,
J.Deisenhofer,
R.Huber.
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Ref.
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J Mol Biol, 1984,
177,
531-557.
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PubMed id
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Abstract
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Two closely related crystal structures of alpha 1-proteinase inhibitor modified
at the reactive site peptide bond Met358--Ser359 have been analysed. The crystal
structure has been obtained from diffraction data at 3 A resolution, with phases
originally from isomorphous replacement. The electron density map was
substantially improved by cyclic averaging of the electron densities of the two
crystal forms and allowed the chain to be traced in terms of the known chemical
amino acid sequence. Energy restrained crystallographic refinement was initiated
and resulted in conventional R-values of 0.251 for the tetragonal crystal form
(6 to 3 A resolution) and 0.247 for the hexagonal crystal form (6 to 3.2 A
resolution). The polypeptide chain is almost completely arranged in well-defined
secondary structural elements: three beta-sheets and eight alpha-helices. The
helices are preferentially formed by the first 150 residues. They are in
proximity underneath sheet A. The chain ends Met358 and Ser359 of the nicked
species are arranged in strands on opposite ends of the molecule indicating a
major structural rearrangement upon modification of the intact inhibitor. It is
suggested that the Met358 strand is in a different conformation removed from
sheet A and approaches Ser359 in the intact inhibitor species. Glu342, which is
exchanged by a lysine in the Z-variant is in a strategic position for such a
rearrangement. The three carbohydrate chains of alpha 1-proteinase inhibitor
have partly defined electron density close to their attachment sites at
asparagine residues. The anti-thrombin and ovalbumin amino acid sequences can be
accommodated in the alpha 1 inhibitor molecular structure. The intron-exon
junctions of the ovalbumin and the alpha 1-proteinase inhibitor gene are all in
surface loops of the mature protein.
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