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3byb

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Current revision

Crystal structure of Textilinin-1, a Kunitz-type serine protease inhibitor from the Australian Common Brown snake venom

Structural highlights

3byb is a 3 chain structure with sequence from Eastern brown snake. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1bpi
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[VKT1_PSETT] Strongly inhibits plasmin (Ki=0.44 nM) and trypsin (Ki=0.42 nM). Has little effect on plasma (Ki=1870 nM) and tissue (Ki=12900 nM) kallikreins. In vivo, reduces bleeding in a small animal model.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Textilinin-1 is a Kunitz-type serine protease inhibitor isolated from the venom of the Australian common brown snake, Pseudonaja textilis. This molecule binds to and blocks the activity of a range of serine proteases, including plasmin and trypsin. Textilinin-1's ability to inhibit plasmin, a protease involved in fibrinolysis, has raised the possibility that it could be used as an alternative to aprotinin (Trasylol) as a systemic antibleeding agent in surgery. Here, the crystal structure of free recombinant textilinin-1 has been determined to 1.63 A, with three molecules observed in the asymmetric unit. All of these have a similar overall fold to aprotinin, except that the canonical loop for one of the molecules is inverted such that the side chain of the P1' residue, Val18, is partially buried by intramolecular contacts to Pro15, Thr13, and Ile36. In aprotinin, the P1' residue is Ala16, whose side chain is too small to form similar contacts. The loop inversion in textilinin-1 is facilitated by changes in backbone dihedral angles for the P1 and P2' residues, such that they alternate between values in the beta-sheet and alpha-helical regions of the Ramachandran plot. In a comparison with the structures of all other known Kunitz-type serine protease inhibitors, no such conformational variability has been observed. The presence of the bulkier valine as the P1' residue in textilinin-1 appears to be a major contributor to reducing the binding affinity for plasmin as compared to aprotinin (3.5 nm versus 0.053 nm) and could also account for an observed narrower binding specificity.

Crystal structure of textilinin-1, a Kunitz-type serine protease inhibitor from the venom of the Australian common brown snake (Pseudonaja textilis).,Millers EK, Trabi M, Masci PP, Lavin MF, de Jersey J, Guddat LW FEBS J. 2009 Jun;276(11):3163-75. Epub 2009 Apr 28. PMID:19490116^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Masci PP, Whitaker AN, Sparrow LG, de Jersey J, Winzor DJ, Watters DJ, Lavin MF, Gaffney PJ. Textilinins from Pseudonaja textilis textilis. Characterization of two plasmin inhibitors that reduce bleeding in an animal model. Blood Coagul Fibrinolysis. 2000 Jun;11(4):385-93. PMID:10847427
↑ Filippovich I, Sorokina N, Masci PP, de Jersey J, Whitaker AN, Winzor DJ, Gaffney PJ, Lavin MF. A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties. Br J Haematol. 2002 Nov;119(2):376-84. PMID:12406072
↑ Flight S, Johnson L, Trabi M, Gaffney P, Lavin M, de Jersey J, Masci P. Comparison of textilinin-1 with aprotinin as serine protease inhibitors and as antifibrinolytic agents. Pathophysiol Haemost Thromb. 2005;34(4-5):188-93. PMID:16707925 doi:http://dx.doi.org/10.1159/000092421
↑ Flight SM, Johnson LA, Du QS, Warner RL, Trabi M, Gaffney PJ, Lavin MF, de Jersey J, Masci PP. Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss. Br J Haematol. 2009 Apr;145(2):207-11. doi: 10.1111/j.1365-2141.2009.07605.x., Epub 2009 Feb 22. PMID:19236611 doi:http://dx.doi.org/10.1111/j.1365-2141.2009.07605.x
↑ Earl ST, Richards R, Johnson LA, Flight S, Anderson S, Liao A, de Jersey J, Masci PP, Lavin MF. Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms. Biochimie. 2012 Feb;94(2):365-73. doi: 10.1016/j.biochi.2011.08.003. Epub 2011, Aug 11. PMID:21843588 doi:http://dx.doi.org/10.1016/j.biochi.2011.08.003
↑ Millers EK, Johnson LA, Birrell GW, Masci PP, Lavin MF, de Jersey J, Guddat LW. The structure of human microplasmin in complex with textilinin-1, an aprotinin-like inhibitor from the Australian brown snake. PLoS One. 2013;8(1):e54104. doi: 10.1371/journal.pone.0054104. Epub 2013 Jan 15. PMID:23335990 doi:10.1371/journal.pone.0054104
↑ Millers EK, Trabi M, Masci PP, Lavin MF, de Jersey J, Guddat LW. Crystal structure of textilinin-1, a Kunitz-type serine protease inhibitor from the venom of the Australian common brown snake (Pseudonaja textilis). FEBS J. 2009 Jun;276(11):3163-75. Epub 2009 Apr 28. PMID:19490116 doi:10.1111/j.1742-4658.2009.07034.x

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3byb"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Textilinin-1, a Kunitz-type serine protease inhibitor from the Australian Common Brown snake venom==
-<StructureSection load='3byb' size='340' side='right' caption='[[3byb]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
+<StructureSection load='3byb' size='340' side='right'caption='[[3byb]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3byb]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Eastern_brown_snake Eastern brown snake]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BYB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3byb]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Eastern_brown_snake Eastern brown snake]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BYB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3BYB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ETX:2-ETHOXYETHANOL'>ETX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ETX:2-ETHOXYETHANOL'>ETX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bpi|1bpi]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3byb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3byb OCA], [http://pdbe.org/3byb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3byb RCSB], [http://www.ebi.ac.uk/pdbsum/3byb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3byb ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3byb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3byb OCA], [http://pdbe.org/3byb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3byb RCSB], [http://www.ebi.ac.uk/pdbsum/3byb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3byb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Eastern brown snake]]
+[[Category: Large Structures]]
 [[Category: Guddat, L W]]
 [[Category: Millers, E K]]

3byb

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Current revision

Crystal structure of Textilinin-1, a Kunitz-type serine protease inhibitor from the Australian Common Brown snake venom

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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