2h5c: Difference between revisions

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[[Image:2h5c.gif|left|200px]]


{{Structure
==0.82A resolution crystal structure of alpha-lytic protease at pH 5==
|PDB= 2h5c |SIZE=350|CAPTION= <scene name='initialview01'>2h5c</scene>, resolution 0.82&Aring;
<StructureSection load='2h5c' size='340' side='right'caption='[[2h5c]], [[Resolution|resolution]] 0.82&Aring;' scene=''>
|SITE=
== Structural highlights ==
|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
<table><tr><td colspan='2'>[[2h5c]] is a 1 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=2H5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H5C FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-lytic_endopeptidase Alpha-lytic endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.12 3.4.21.12] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.82&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5c OCA], [https://pdbe.org/2h5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h5c RCSB], [https://www.ebi.ac.uk/pdbsum/2h5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h5c ProSAT]</span></td></tr>
|RELATEDENTRY=[[1ssx|1SSX]], [[1tal|1TAL]], [[2ull|2ULL]], [[1qrx|1QRX]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5c OCA], [http://www.ebi.ac.uk/pdbsum/2h5c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h5c RCSB]</span>
== 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/h5/2h5c_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=2h5c 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.


'''0.82A resolution crystal structure of alpha-lytic protease at pH 5'''
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2h5c" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Alpha-lytic protease 3D structures|Alpha-lytic protease 3D structures]]
 
== References ==
==About this Structure==
<references/>
2H5C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5C OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Large Structures]]
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:[http://www.ncbi.nlm.nih.gov/pubmed/16834383 16834383]
[[Category: Alpha-lytic endopeptidase]]
[[Category: Lysobacter enzymogenes]]
[[Category: Lysobacter enzymogenes]]
[[Category: Single protein]]
[[Category: Agard DA]]
[[Category: Agard, D A.]]
[[Category: Daugherty MD]]
[[Category: Daugherty, M D.]]
[[Category: Fuhrmann CN]]
[[Category: Fuhrmann, C N.]]
[[Category: a-lytic protease]]
[[Category: acylation transition state]]
[[Category: catalysis]]
[[Category: packing distortion]]
[[Category: protein folding]]
[[Category: protein stability]]
[[Category: serine protease]]
[[Category: ultra-high resolution]]
 
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Retrieved from "https://proteopedia.org/2h5c"