1a5i: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (20 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==CATALYTIC DOMAIN OF VAMPIRE BAT (DESMODUS ROTUNDUS) SALIVA PLASMINOGEN ACTIVATOR IN COMPLEX WITH EGR-CMK (GLU-GLY-ARG CHLOROMETHYL KETONE)== | ||
The saliva of the blood-eating vampire bat Desmodus rotundus contains | <StructureSection load='1a5i' size='340' side='right'caption='[[1a5i]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1a5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Desmodus_rotundus Desmodus rotundus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A5I FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1a5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a5i OCA], [https://pdbe.org/1a5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a5i RCSB], [https://www.ebi.ac.uk/pdbsum/1a5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a5i ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/URT1_DESRO URT1_DESRO] Probably essential to support the feeding habits of this exclusively haematophagous animal. Potent thrombolytic agent. | |||
== 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/a5/1a5i_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1a5i ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The saliva of the blood-eating vampire bat Desmodus rotundus contains plasminogen activators (PAs) that maintain the fluidity of the prey's blood by activating plasminogen and dissolving developing fibrin clots. D. rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved domains reminiscent of human tissue-type PA (tPA), but their catalytic domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl ketone and its structure solved at 2.9 A resolution. The structure is similar to that of activated two-chain human tPA. Despite its single-chain status, the activation domain is observed in an enzymatically active conformation, with a functional substrate binding site and active site accommodating the peptidylmethylene inhibitor. The activation pocket, which normally receives the N-terminal Ile16, is occupied by the side chain of Lys156, whose distal ammonium group makes an internal salt bridge with the carboxylate group of Asp194. Lys156 is in a groove shielded from the bulk solvent by the intact "activation loop" (Gln10-Phe21), favoring Lys156-Asp194 salt bridge formation and stabilization of a functional substrate binding site. Together with the characteristic 186 insertion loop, the activation loop could act as a switch, effecting full single-chain enzymatic activity upon binding to fibrin. | |||
Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.,Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W Biochemistry. 1997 Nov 4;36(44):13483-93. PMID:9354616<ref>PMID:9354616</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1a5i" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Plasminogen activator|Plasminogen activator]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Desmodus rotundus]] | [[Category: Desmodus rotundus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bode W]] | |||
[[Category: Bode | [[Category: Renatus M]] | ||
[[Category: Renatus | [[Category: Stubbs MT]] | ||
[[Category: Stubbs | |||
Latest revision as of 09:21, 30 October 2024
CATALYTIC DOMAIN OF VAMPIRE BAT (DESMODUS ROTUNDUS) SALIVA PLASMINOGEN ACTIVATOR IN COMPLEX WITH EGR-CMK (GLU-GLY-ARG CHLOROMETHYL KETONE)CATALYTIC DOMAIN OF VAMPIRE BAT (DESMODUS ROTUNDUS) SALIVA PLASMINOGEN ACTIVATOR IN COMPLEX WITH EGR-CMK (GLU-GLY-ARG CHLOROMETHYL KETONE)
Structural highlights
FunctionURT1_DESRO Probably essential to support the feeding habits of this exclusively haematophagous animal. Potent thrombolytic agent. 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 PubMedThe saliva of the blood-eating vampire bat Desmodus rotundus contains plasminogen activators (PAs) that maintain the fluidity of the prey's blood by activating plasminogen and dissolving developing fibrin clots. D. rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved domains reminiscent of human tissue-type PA (tPA), but their catalytic domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl ketone and its structure solved at 2.9 A resolution. The structure is similar to that of activated two-chain human tPA. Despite its single-chain status, the activation domain is observed in an enzymatically active conformation, with a functional substrate binding site and active site accommodating the peptidylmethylene inhibitor. The activation pocket, which normally receives the N-terminal Ile16, is occupied by the side chain of Lys156, whose distal ammonium group makes an internal salt bridge with the carboxylate group of Asp194. Lys156 is in a groove shielded from the bulk solvent by the intact "activation loop" (Gln10-Phe21), favoring Lys156-Asp194 salt bridge formation and stabilization of a functional substrate binding site. Together with the characteristic 186 insertion loop, the activation loop could act as a switch, effecting full single-chain enzymatic activity upon binding to fibrin. Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.,Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W Biochemistry. 1997 Nov 4;36(44):13483-93. PMID:9354616[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||