4l6g: Difference between revisions
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==Crystal Structure of P450cin Y81F mutant, crystallized in 7 mM 1,8-cineole== | |||
<StructureSection load='4l6g' size='340' side='right'caption='[[4l6g]], [[Resolution|resolution]] 1.37Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4l6g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_braakii Citrobacter braakii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L6G 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]] 1.371Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CNL:1,3,3-TRIMETHYL-2-OXABICYCLO[2.2.2]OCTANE'>CNL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4l6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l6g OCA], [https://pdbe.org/4l6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l6g RCSB], [https://www.ebi.ac.uk/pdbsum/4l6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l6g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CINA_CITBR CINA_CITBR] Involved in the degradation of cineol (eucalyptol). Catalyzes the initial hydroxylation of cineole exclusively at the pro-R carbon to give the (S)-6beta-hydroxycineole. Cineole is the natural substrate of CinA. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In P450cin, Tyr81, Asp241, Asn242, two water molecules, and the substrate participate in a complex H-bonded network. The role of this H-bonded network in substrate binding and catalysis has been probed by crystallography, spectroscopy, kinetics, isothermal titration calorimetry (ITC), and molecular dynamics. For the Y81F mutant, the substrate binds about 20-fold more weakly and Vmax decreases by about 30% in comparison to WT. The enhanced susceptibility of the heme to H2O2-mediated destruction in Y81F suggests that this mutant favors the open, low-spin conformational state. Asn242 H-bonds directly with the substrate, and replacing this residue with Ala results in water taking the place of the missing Asn side chain. This mutant exhibits a 70% decrease in activity. Crystal structures and molecular dynamics simulations of substrate-bound complexes show that the solvent has more ready access to the active site, especially for the N242A mutant. This accounts for about a 64% uncoupling of electron transfer from substrate hydroxylation. These data indicate the importance of the interconnected water network on substrate binding and on the open/closed conformational equilibrium, which are both critically important for maintaining high-coupling efficiency. | |||
P450cin Active Site Water: Implications for Substrate Binding and Solvent Accessibility.,Madrona Y, Hollingsworth SA, Khan B, Poulos TL Biochemistry. 2013 Jul 18. PMID:23829586<ref>PMID:23829586</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4l6g" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Citrobacter braakii]] | |||
[[Category: Large Structures]] | |||
[[Category: Madrona Y]] | |||
[[Category: Poulos TL]] | |||