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.


1g36

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1g36" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g36, resolution 1.90&Aring;" /> '''TRYPSIN INHIBITOR CO...)
Current revision (11:19, 27 March 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1g36.jpg|left|200px]]<br /><applet load="1g36" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1g36, resolution 1.90&Aring;" />
 
-
'''TRYPSIN INHIBITOR COMPLEX'''<br />
 
-
==Overview==
+
==TRYPSIN INHIBITOR COMPLEX==
-
BACKGROUND: A major current focus of pharmaceutical research is the, development of selective inhibitors of the blood coagulation enzymes, thrombin or factor Xa to be used as orally bioavailable anticoagulant, drugs in thromboembolic disorders and in the prevention of venous and, arterial thrombosis. Simultaneous direct inhibition of thrombin and factor, Xa by synthetic proteinase inhibitors as a novel approach to, antithrombotic therapy could result in potent anticoagulants with improved, pharmacological properties. RESULTS: The binding mode of such dual, specific inhibitors of thrombin and factor Xa was determined for the first, time by comparative crystallography using human alpha-thrombin, human, des-Gla (1--44) factor Xa and bovine trypsin as the ligand receptors. The, benzamidine-based inhibitors utilize two different conformations for the, interaction with thrombin and factor Xa/trypsin, which are evoked by the, steric requirements of the topologically different S2 subsites of the, enzymes. Compared to the unliganded forms of the proteinases, ligand, binding induces conformational adjustments of thrombin and factor Xa, active site residues indicative of a pronounced induced fit mechanism., CONCLUSION: The structural data reveal the molecular basis for a desired, unselective inhibition of the two key components of the blood coagulation, cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine, moieties of the inhibitors are able to fill both the small solvent, accessible as well as the larger hydrophobic S2 pockets of factor Xa and, thrombin, respectively. Distal fragments of the inhibitors are identified, which fit into both the cation hole/aromatic box of factor Xa and the, hydrophobic aryl binding site of thrombin. Thus, binding constants in the, medium-to-low nanomolar range are obtained against both enzymes.
+
<StructureSection load='1g36' size='340' side='right'caption='[[1g36]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-
 
+
== Structural highlights ==
-
==About this Structure==
+
<table><tr><td colspan='2'>[[1g36]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G36 FirstGlance]. <br>
-
1G36 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CA, SO4 and R11 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1G36 OCA].
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-
 
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=R11:4-{[1-METHYL-5-(2-METHYL-BENZOIMIDAZOL-1-YLMETHYL)-1H-BENZOIMIDAZOL-2-YLMETHYL]-AMINO}-BENZAMIDINE'>R11</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
==Reference==
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g36 OCA], [https://pdbe.org/1g36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g36 RCSB], [https://www.ebi.ac.uk/pdbsum/1g36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g36 ProSAT]</span></td></tr>
-
Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors., Nar H, Bauer M, Schmid A, Stassen JM, Wienen W, Priepke HW, Kauffmann IK, Ries UJ, Hauel NH, Structure. 2001 Jan 10;9(1):29-37. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11342132 11342132]
+
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN]
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/1g36_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1g36 ConSurf].
 +
<div style="clear:both"></div>
 +
__TOC__
 +
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Trypsin]]
+
[[Category: Nar H]]
-
[[Category: Nar, H.]]
+
-
[[Category: CA]]
+
-
[[Category: R11]]
+
-
[[Category: SO4]]
+
-
[[Category: blood coagulation]]
+
-
[[Category: blood coagulation cascade]]
+
-
[[Category: factor xa]]
+
-
[[Category: inhibitor complexes]]
+
-
[[Category: serine proteinase]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:39:44 2007''
+

Current revision

TRYPSIN INHIBITOR COMPLEX

PDB ID 1g36

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1g36"
Personal tools