1ttc: Difference between revisions
New page: left|200px<br /> <applet load="1ttc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ttc, resolution 1.7Å" /> '''THE X-RAY CRYSTAL ST... |
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[[Image:1ttc.gif|left|200px]]<br /> | [[Image:1ttc.gif|left|200px]]<br /><applet load="1ttc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1ttc, resolution 1.7Å" /> | caption="1ttc, resolution 1.7Å" /> | ||
'''THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION'''<br /> | '''THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
The x-ray crystal structures of normal human transthyretin (prealbumin) | The x-ray crystal structures of normal human transthyretin (prealbumin) and the amyloidogenic Val-30-Met variant have been refined at 1.7-A resolution to R-values of 0.168 and 0.179, respectively, for 19,882 and 20,362 reflections (Fobs > 2.0 sigma). Standard deviations for stereochemical parameters are 0.018 and 0.022 A for bond distances, 0.030 and 0.038 A for angle distances, and 0.035 and 0.070 A for planar 1-4 distances. The newly refined normal structure shows improvement over the original structure of Blake and Swan (Blake, C. C. F., and Swan, I. D. A. (1971) J. Mol. Biol. 61, 217-224) in stereochemistry and in the conformation of the loop regions. Residues Arg-103, Thr-123, Asn-124, and Pro-125 have now been resolved, and residues 1-9 and 126-127 have been modeled with the aid of simulated annealing refinement. The functional form of transthyretin is a tetramer, having a cylindrical cavity which will bind thyroxine and an exterior binding site for the complex of retinol with retinol-binding protein. The monomer is a beta barrel flattened to become more like a sandwich with residue 30 in the interior. The methionyl for valyl substitution forces the beta sheets of the monomer as much as 1 A apart, resulting in a distortion of the thyroxine-binding cavity, in agreement with the independent observations that the Met-30 variant has low affinity for thyroxine. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1TTC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1TTC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Braden, B | [[Category: Braden, B C.]] | ||
[[Category: Hamilton, J | [[Category: Hamilton, J A.]] | ||
[[Category: Steinrauf, L | [[Category: Steinrauf, L K.]] | ||
[[Category: transport(thyroxine)]] | [[Category: transport(thyroxine)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:06 2008'' | ||
Revision as of 16:17, 21 February 2008
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THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION
OverviewOverview
The x-ray crystal structures of normal human transthyretin (prealbumin) and the amyloidogenic Val-30-Met variant have been refined at 1.7-A resolution to R-values of 0.168 and 0.179, respectively, for 19,882 and 20,362 reflections (Fobs > 2.0 sigma). Standard deviations for stereochemical parameters are 0.018 and 0.022 A for bond distances, 0.030 and 0.038 A for angle distances, and 0.035 and 0.070 A for planar 1-4 distances. The newly refined normal structure shows improvement over the original structure of Blake and Swan (Blake, C. C. F., and Swan, I. D. A. (1971) J. Mol. Biol. 61, 217-224) in stereochemistry and in the conformation of the loop regions. Residues Arg-103, Thr-123, Asn-124, and Pro-125 have now been resolved, and residues 1-9 and 126-127 have been modeled with the aid of simulated annealing refinement. The functional form of transthyretin is a tetramer, having a cylindrical cavity which will bind thyroxine and an exterior binding site for the complex of retinol with retinol-binding protein. The monomer is a beta barrel flattened to become more like a sandwich with residue 30 in the interior. The methionyl for valyl substitution forces the beta sheets of the monomer as much as 1 A apart, resulting in a distortion of the thyroxine-binding cavity, in agreement with the independent observations that the Met-30 variant has low affinity for thyroxine.
DiseaseDisease
Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]
About this StructureAbout this Structure
1TTC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution., Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L, J Biol Chem. 1993 Feb 5;268(4):2416-24. PMID:8428915
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