View source for 7or2


==Crystal structure of UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) from Pseudomonas aeruginosa in complex with FAD and a pyrazole derivative (fragment 4)==
<StructureSection load='7or2' size='340' side='right'caption='[[7or2]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7or2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OR2 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9FH:5-methyl-1-phenyl-pyrazole-4-carboxylic+acid'>9FH</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=7or2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7or2 OCA], [https://pdbe.org/7or2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7or2 RCSB], [https://www.ebi.ac.uk/pdbsum/7or2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7or2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MURB_PSEAE MURB_PSEAE] Cell wall formation (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pseudomonas aeruginosa is of major concern for cystic fibrosis patients where this infection can be fatal. With the emergence of drug-resistant strains, there is an urgent need to develop novel antibiotics against P. aeruginosa. MurB is a promising target for novel antibiotic development as it is involved in the cell wall biosynthesis. MurB has been shown to be essential in P. aeruginosa, and importantly, no MurB homologue exists in eukaryotic cells. A fragment-based drug discovery approach was used to target Pa MurB. This led to the identification of a number of fragments, which were shown to bind to MurB. One fragment, a phenylpyrazole scaffold, was shown by ITC to bind with an affinity of Kd = 2.88 mM (LE 0.23). Using a structure guided approach, different substitutions were synthesized and the initial fragment was optimized to obtain a small molecule with Kd = 3.57 muM (LE 0.35).

Discovery of Novel Inhibitors of Uridine Diphosphate-N-Acetylenolpyruvylglucosamine Reductase (MurB) from Pseudomonas aeruginosa, an Opportunistic Infectious Agent Causing Death in Cystic Fibrosis Patients.,Acebron-Garcia-de-Eulate M, Mayol-Llinas J, Holland MTO, Kim SY, Brown KP, Marchetti C, Hess J, Di Pietro O, Mendes V, Abell C, Floto RA, Coyne AG, Blundell TL J Med Chem. 2022 Jan 26. doi: 10.1021/acs.jmedchem.1c01684. PMID:35080396<ref>PMID:35080396</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7or2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Abell C]]
[[Category: Acebron-Garcia de Eulate M]]
[[Category: Blundell TL]]
[[Category: Kim SY]]
[[Category: Mendes V]]