1dzh

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{{STRUCTURE_1dzh| PDB=1dzh | SCENE= }}
{{STRUCTURE_1dzh| PDB=1dzh | SCENE= }}
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'''P14-FLUORESCEIN-N135Q-S380C-ANTITHROMBIN-III'''
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===P14-FLUORESCEIN-N135Q-S380C-ANTITHROMBIN-III===
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==Overview==
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Antithrombin is unique among the serpins in that it circulates in a native conformation that is kinetically inactive toward its target proteinase, factor Xa. Activation occurs upon binding of a specific pentasaccharide sequence found in heparin that results in a rearrangement of the reactive center loop removing constraints on the active center P1 residue. We determined the crystal structure of an activated antithrombin variant, N135Q S380C-fluorescein (P14-fluorescein), in order to see how full activation is achieved in the absence of heparin and how the structural effects of the substitution in the hinge region are translated to the heparin binding region. The crystal structure resembles native antithrombin except in the hinge and heparin binding regions. The absence of global conformational change allows for identification of specific interactions, centered on Glu(381) (P13), that are responsible for maintenance of the solution equilibrium between the native and activated forms and establishes the existence of an electrostatic link between the hinge region and the heparin binding region. A revised model for the mechanism of the allosteric activation of antithrombin is proposed.
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(as it appears on PubMed at http://www.pubmed.gov), where 10809774 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10809774}}
==About this Structure==
==About this Structure==
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[[Category: Mccoy, A J.]]
[[Category: Mccoy, A J.]]
[[Category: Serpin]]
[[Category: Serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:28:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:53:23 2008''

Revision as of 20:53, 30 June 2008

Image:1dzh.png

Template:STRUCTURE 1dzh

P14-FLUORESCEIN-N135Q-S380C-ANTITHROMBIN-III

Template:ABSTRACT PUBMED 10809774

About this Structure

1DZH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The conformational activation of antithrombin. A 2.85-A structure of a fluorescein derivative reveals an electrostatic link between the hinge and heparin binding regions., Huntington JA, McCoy A, Belzar KJ, Pei XY, Gettins PG, Carrell RW, J Biol Chem. 2000 May 19;275(20):15377-83. PMID:10809774

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