Crystal Structure of Thrombin in Complex with S-Variegin: Insights of a Novel Mechanism of Inhibition and Design of Tunable Thrombin Inhibitors Page: 2
The following text was automatically extracted from the image on this page using optical character recognition software:
A Novel Mechanism of Thrombin Inhibition
Figure 1. Structure of thrombin:s-variegin complex. (A) Thrombin (yellow) shown in the classical orientation in ribbon (without s-variegin).
Side chains of catalytic triad, TAspI02, THis57 and TSerl95 are shown in sticks (green). The 60-loop, autolysis loop and Na+-binding loop are circled in
brown, cyan and green, respectively. Parts of thrombin forming the anion-binding exosite-I and exosite-ll are circled in blue and purple, respectively.
(B) Surface representation of thrombin (yellow) in the same orientation as (a). Locations of active site specificity pocket, non-prime and prime subsites
are indicated by arrows. (C) The structure of thrombin (yellow) in the same orientation as above shown in complex with s-variegin (pink) together
with its electron density map (2Fo-Fc) shown contoured at 0.9c. (D) Surface representation of thrombin in complex with s-variegin (pink).
is one of the main targets for inhibition, owing to its pivotal role in
coagulation. Several direct thrombin inhibitors, such as hirudin
, hirulog- 1/bivalirudin , argatroban  and dabigatran
, are currently available in the market. Among them, hirudin
and hirulog-1 /bivalirudin are both developed from hematopha-
gous parasites and their success continues to inspire the search for
more novel anticoagulants from these sources [14,15].
: PLoS ONE I www.plosone.org
Recently, we described variegin, a novel, fast and tight-binding
competitive inhibitor of thrombin (refers to the a form of thrombin
unless otherwise stated) isolated from the tropical bont tick,
Ambdyomma variegatum . Like hirudin/hirulog, variegin targets
the thrombin catalytic site and exosite-I. However, unlike other
naturally occurring thrombin inhibitors, variegin interacts with the
thrombin prime subsites in addition to exosite-I . Variegin has
October 2011 1 Volume 6 1 Issue 10 1 e26367
Here’s what’s next.
This article can be searched. Note: Results may vary based on the legibility of text within the document.
Tools / Downloads
Get a copy of this page or view the extracted text.
Citing and Sharing
Basic information for referencing this web page. We also provide extended guidance on usage rights, references, copying or embedding.
Reference the current page of this Article.
Koh, Cho Yeow; Kumar, Sundramurthy; Kazimirova, Maria; Nuttall, Patricia A.; Radhakrishnan, Uvaraj P.; Kim, Seongcheol et al. Crystal Structure of Thrombin in Complex with S-Variegin: Insights of a Novel Mechanism of Inhibition and Design of Tunable Thrombin Inhibitors, article, October 2011; [San Francisco, California]. (digital.library.unt.edu/ark:/67531/metadc287041/m1/2/: accessed January 18, 2019), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.