1h46: Difference between revisions
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New page: left|200px<br /> <applet load="1h46" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h46, resolution 1.52Å" /> '''THE CATALYTIC MODUL... |
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== | ==The catalytic module of Cel7D from Phanerochaete chrysosporium as a chiral selector: Structural studies of its complex with the b-blocker (R)-propranolol== | ||
Previous investigations have shown that the major cellobiohydrolase of | <StructureSection load='1h46' size='340' side='right'caption='[[1h46]], [[Resolution|resolution]] 1.52Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1h46]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Phanerodontia_chrysosporium Phanerodontia chrysosporium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H46 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]] 1.52Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=RNP:(1E,2R)-1-(ISOPROPYLIMINO)-3-(1-NAPHTHYLOXY)PROPAN-2-OL'>RNP</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=1h46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h46 OCA], [https://pdbe.org/1h46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h46 RCSB], [https://www.ebi.ac.uk/pdbsum/1h46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h46 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7LHI2_PHACH Q7LHI2_PHACH] | |||
== 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/h4/1h46_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=1h46 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Previous investigations have shown that the major cellobiohydrolase of Phanerochaete chrysosporium, Cel7D (CBH 58), can be used to separate the enantiomers of a number of drugs, including adrenergic beta blockers such as propranolol. The structural basis of this enantioselectivity is explored here. A 1.5 A X-ray structure of the catalytic domain of Cel7D in complex with (R)-propranolol showed the ligand bound at the active site in glucosyl-binding subsites -1/+1. The catalytic residue Glu207 makes a strong charge-charge interaction with the secondary amine of (R)-propranolol; this is supported by a second interaction of the amine with the nearby Asp209. The aromatic naphthyl group stacks onto the indole ring of Trp373 (normally the glucosyl-binding platform of subsite +1). Other factors also contribute to good complementarity between the ligand and the substrate-binding cleft of the enzyme. Comparison with the previous structure of a related cellulase, Cel7A from Trichoderma reesei, in complex with (S)-propranolol strongly suggests that these enzymes will bind the (S)-enantiomer in a very similar manner, distinct from their mode of binding to (R)-propranolol. Tighter binding of both enzymes to the (S)-enantiomer is largely explained by two additional hydrogen-bonding interactions with its hydroxyl group. The distinct preference for the (R)-enantiomer is probably a consequence of structural differences near the naphthyl group of the ligand. | |||
The catalytic module of Cel7D from Phanerochaete chrysosporium as a chiral selector: structural studies of its complex with the beta blocker (R)-propranolol.,Munoz IG, Mowbray SL, Stahlberg J Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):637-43. Epub 2003, Mar 25. PMID:12657782<ref>PMID:12657782</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1h46" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cellobiohydrolase 3D structures|Cellobiohydrolase 3D structures]] | |||
*[[Glucanase 3D structures|Glucanase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Phanerodontia chrysosporium]] | |||
[[Category: Mowbray SL]] | |||
[[Category: Munoz IG]] | |||
[[Category: Stahlberg J]] | |||
