View source for 7fjh


==LecA from Pseudomonas aeruginosa in complex with 4-Phenylbutyryl hydroxamic acid (CAS: 32153-46-1)==
<StructureSection load='7fjh' size='340' side='right'caption='[[7fjh]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7fjh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FJH 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]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R9:N-oxidanyl-4-phenyl-butanamide'>4R9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=7fjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fjh OCA], [https://pdbe.org/7fjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fjh RCSB], [https://www.ebi.ac.uk/pdbsum/7fjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fjh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PA1L_PSEAE PA1L_PSEAE] D-galactose specific lectin. Binds in decreasing order of affinity: melibiose, methyl-alpha-D-galactoside, D-galactose, methyl-beta-D-galactoside, N-acetyl-D-galactosamine. Similar to plant lectins in its selective (carbohydrate-specific) hemagglutinating activity.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Carbohydrate-protein interactions are key for cell-cell and host-pathogen recognition and thus, emerged as viable therapeutic targets. However, their hydrophilic nature poses major limitations to the conventional development of drug-like inhibitors. To address this shortcoming, four fragment libraries were screened to identify metal-binding pharmacophores (MBPs) as novel scaffolds for inhibition of Ca(2+)-dependent carbohydrate-protein interactions. Here, we show the effect of MBPs on the clinically relevant lectins DC-SIGN, Langerin, LecA and LecB. Detailed structural and biochemical investigations revealed the specificity of MBPs for different Ca(2+)-dependent lectins. Exploring the structure-activity relationships of several fragments uncovered the functional groups in the MBPs suitable for modification to further improve lectin binding and selectivity. Selected inhibitors bound efficiently to DC-SIGN-expressing cells. Altogether, the discovery of MBPs as a promising class of Ca(2+)-dependent lectin inhibitors creates a foundation for fragment-based ligand design for future drug discovery campaigns.

Targeting undruggable carbohydrate recognition sites through focused fragment library design.,Shanina E, Kuhaudomlarp S, Siebs E, Fuchsberger FF, Denis M, da Silva Figueiredo Celestino Gomes P, Clausen MH, Seeberger PH, Rognan D, Titz A, Imberty A, Rademacher C Commun Chem. 2022 May 20;5(1):64. doi: 10.1038/s42004-022-00679-3. PMID:36697615<ref>PMID:36697615</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7fjh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Galactose-binding lectin|Galactose-binding lectin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Clausen MH]]
[[Category: Denis M]]
[[Category: Fuchsberger F]]
[[Category: Imberty A]]
[[Category: Kuhaudomlarp S]]
[[Category: Rademacher C]]
[[Category: Rognan D]]
[[Category: Seeberger PH]]
[[Category: Shanina S]]
[[Category: Siebs E]]
[[Category: Titz A]]
[[Category: Da Silva Figueiredo Celstino Gomes P]]