4l9p: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4l9p]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L9P FirstGlance]. <br>
<table><tr><td colspan='2'>[[4l9p]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L9P FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FII:[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC+ACID'>FII</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4l9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l9p OCA], [https://pdbe.org/4l9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l9p RCSB], [https://www.ebi.ac.uk/pdbsum/4l9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l9p ProSAT]</span></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=4l9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l9p OCA], [https://pdbe.org/4l9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l9p RCSB], [https://www.ebi.ac.uk/pdbsum/4l9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l9p ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/Q4WP27_ASPFU Q4WP27_ASPFU]  
[https://www.uniprot.org/uniprot/Q4WP27_ASPFU Q4WP27_ASPFU]  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Species of the fungal genus Aspergillus are significant human and agricultural pathogens that are often refractory to existing antifungal treatments. Protein farnesyltransferase (FTase), a critical enzyme in eukaryotes, is an attractive potential target for antifungal drug discovery. We report high-resolution structures of A. fumigatus FTase (AfFTase) in complex with substrates and inhibitors. Comparison of structures with farnesyldiphosphate (FPP) bound in the absence or presence of peptide substrate, corresponding to successive steps in ordered substrate binding, revealed that the second substrate-binding step is accompanied by motions of a loop in the catalytic site. Re-examination of other FTase structures showed that this motion is conserved. The substrate- and product-binding clefts in the AfFTase active site are wider than in human FTase (hFTase). Widening is a consequence of small shifts in the alpha-helices that comprise the majority of the FTase structure, which in turn arise from sequence variation in the hydrophobic core of the protein. These structural effects are key features that distinguish fungal FTases from hFTase. Their variation results in differences in steady-state enzyme kinetics and inhibitor interactions, and presents opportunities for developing selective anti-fungal drugs by exploiting size differences in the active sites. We illustrate the latter by comparing the interaction of ED5 and Tipifarnib with hFTase and AfFTase. In AfFTase the wider groove enables ED5 to bind in the presence of FPP, whereas in hFTase it binds only in the absence of substrate. Tipifarnib binds similarly to both enzymes, but makes less extensive contacts in AfFTase with consequently weaker binding.
Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design.,Mabanglo MF, Hast MA, Lubock NB, Hellinga HW, Beese LS Protein Sci. 2013 Dec 17. doi: 10.1002/pro.2411. PMID:24347326<ref>PMID:24347326</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4l9p" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
== References ==
<references/>
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</StructureSection>
</StructureSection>

Latest revision as of 12:18, 1 March 2024

Crystal structure of Aspergillus fumigatus protein farnesyltransferase complexed with the FII analog, FPT-II, and the KCVVM peptide

4l9p, resolution 1.45Å

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