2h5d: Difference between revisions
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New page: left|200px<br /><applet load="2h5d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h5d, resolution 0.90Å" /> '''0.9A resolution crys... |
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== | ==0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid== | ||
To address questions regarding the mechanism of serine protease catalysis, we have solved two X-ray crystal structures of alpha-lytic protease | <StructureSection load='2h5d' size='340' side='right'caption='[[2h5d]], [[Resolution|resolution]] 0.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2h5d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H5D 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]] 0.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B2V:VALINE+BORONIC+ACID'>B2V</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSU:SUCCINIC+ACID+MONOMETHYL+ESTER'>MSU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2h5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5d OCA], [https://pdbe.org/2h5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h5d RCSB], [https://www.ebi.ac.uk/pdbsum/2h5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h5d ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PRLA_LYSEN PRLA_LYSEN] | |||
== 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/h5/2h5d_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=2h5d ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
To address questions regarding the mechanism of serine protease catalysis, we have solved two X-ray crystal structures of alpha-lytic protease (alphaLP) that mimic aspects of the transition states: alphaLP at pH 5 (0.82 A resolution) and alphaLP bound to the peptidyl boronic acid inhibitor, MeOSuc-Ala-Ala-Pro-boroVal (0.90 A resolution). Based on these structures, there is no evidence of, or requirement for, histidine-flipping during the acylation step of the reaction. Rather, our data suggests that upon protonation of His57, Ser195 undergoes a conformational change that destabilizes the His57-Ser195 hydrogen bond, preventing the back-reaction. In both structures the His57-Asp102 hydrogen bond in the catalytic triad is a normal ionic hydrogen bond, and not a low-barrier hydrogen bond (LBHB) as previously hypothesized. We propose that the enzyme has evolved a network of relatively short hydrogen bonds that collectively stabilize the transition states. In particular, a short ionic hydrogen bond (SIHB) between His57 Nepsilon2 and the substrate's leaving group may promote forward progression of the TI1-to-acylenzyme reaction. We provide experimental evidence that refutes use of either a short donor-acceptor distance or a downfield 1H chemical shift as sole indicators of a LBHB. | |||
Subangstrom crystallography reveals that short ionic hydrogen bonds, and not a His-Asp low-barrier hydrogen bond, stabilize the transition state in serine protease catalysis.,Fuhrmann CN, Daugherty MD, Agard DA J Am Chem Soc. 2006 Jul 19;128(28):9086-102. PMID:16834383<ref>PMID:16834383</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | <div class="pdbe-citations 2h5d" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Alpha-lytic protease 3D structures|Alpha-lytic protease 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lysobacter enzymogenes]] | [[Category: Lysobacter enzymogenes]] | ||
[[Category: Agard DA]] | |||
[[Category: Agard | [[Category: Fuhrmann CN]] | ||
[[Category: Fuhrmann | |||
Latest revision as of 01:00, 21 November 2024
0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid
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