View source for 6isr


==structure of lipase mutant with Cys-His-Asp catalytic triad==
<StructureSection load='6isr' size='340' side='right'caption='[[6isr]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6isr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Moesziomyces_antarcticus Moesziomyces antarcticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ISR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ISR 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=6isr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6isr OCA], [https://pdbe.org/6isr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6isr RCSB], [https://www.ebi.ac.uk/pdbsum/6isr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6isr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIPB_PSEA2 LIPB_PSEA2] Hydrolysis of triglycerides. Is very stereospecific both in hydrolysis and in organic synthesis and has a potentially important application in glucolipid synthesis.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser --&gt; Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105(-)/His224(+) rather than a concerted process.

Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution.,Cen Y, Singh W, Arkin M, Moody TS, Huang M, Zhou J, Wu Q, Reetz MT Nat Commun. 2019 Jul 19;10(1):3198. doi: 10.1038/s41467-019-11155-3. PMID:31324776<ref>PMID:31324776</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6isr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lipase 3D Structures|Lipase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Moesziomyces antarcticus]]
[[Category: Cen YX]]
[[Category: Wu Q]]
[[Category: Zhou JH]]