This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1sgi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1sgi.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1sgi.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1sgi| PDB=1sgi | SCENE= }}
{{STRUCTURE_1sgi| PDB=1sgi | SCENE= }}
-
'''Crystal structure of the anticoagulant slow form of thrombin'''
+
===Crystal structure of the anticoagulant slow form of thrombin===
-
==Overview==
+
<!--
-
Na(+) binding near the primary specificity pocket of thrombin promotes the procoagulant, prothrombotic, and signaling functions of the enzyme. The effect is mediated allosterically by a communication between the Na(+) site and regions involved in substrate recognition. Using a panel of 78 Ala mutants of thrombin, we have mapped the allosteric core of residues that are energetically linked to Na(+) binding. These residues are Asp-189, Glu-217, Asp-222, and Tyr-225, all in close proximity to the bound Na(+). Among these residues, Asp-189 shares with Asp-221 the important function of transducing Na(+) binding into enhanced catalytic activity. None of the residues of exosite I, exosite II, or the 60-loop plays a significant role in Na(+) binding and allosteric transduction. X-ray crystal structures of the Na(+)-free (slow) and Na(+)-bound (fast) forms of thrombin, free or bound to the active site inhibitor H-d-Phe-Pro-Arg-chloromethyl-ketone, document the conformational changes induced by Na(+) binding. The slow --&gt; fast transition results in formation of the Arg-187:Asp-222 ion pair, optimal orientation of Asp-189 and Ser-195 for substrate binding, and a significant shift of the side chain of Glu-192 linked to a rearrangement of the network of water molecules that connect the bound Na(+) to Ser-195 in the active site. The changes in the water network and the allosteric core explain the thermodynamic signatures linked to Na(+) binding and the mechanism of thrombin activation by Na(+). The role of the water network uncovered in this study establishes a new paradigm for the allosteric regulation of thrombin and other Na(+)-activated enzymes involved in blood coagulation and the immune response.
+
The line below this paragraph, {{ABSTRACT_PUBMED_15152000}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 15152000 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_15152000}}
==Disease==
==Disease==
Line 36: Line 40:
[[Category: Allostery]]
[[Category: Allostery]]
[[Category: Thrombin]]
[[Category: Thrombin]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:40:25 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:58:23 2008''

Revision as of 23:58, 28 July 2008

Image:1sgi.png

Template:STRUCTURE 1sgi

Contents

Crystal structure of the anticoagulant slow form of thrombin

Template:ABSTRACT PUBMED 15152000

Disease

Known disease associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1SGI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Molecular dissection of Na+ binding to thrombin., Pineda AO, Carrell CJ, Bush LA, Prasad S, Caccia S, Chen ZW, Mathews FS, Di Cera E, J Biol Chem. 2004 Jul 23;279(30):31842-53. Epub 2004 May 19. PMID:15152000

Page seeded by OCA on Tue Jul 29 02:58:23 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sgi"
Personal tools