View source for 4c13


==x-ray crystal structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lys==
<StructureSection load='4c13' size='340' side='right'caption='[[4c13]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4c13]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C13 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]] 1.9&#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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UML:URIDINE+5DIPHOSPHO+N-ACETYL+MURAMOYL-L-ALANYL-D-GLUTAMYL-L-LYSINE'>UML</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=4c13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c13 OCA], [https://pdbe.org/4c13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c13 RCSB], [https://www.ebi.ac.uk/pdbsum/4c13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c13 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MURE_STAA8 MURE_STAA8] Catalyzes the addition of L-lysine to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan. Can not use diaminopimelate as substrate. Seems to have a role in beta-lactam antibiotic resistance.<ref>PMID:14114846</ref> <ref>PMID:10498701</ref> <ref>PMID:14996801</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor. More importantly, the inhibition of only the enzymatic function of CDK2 would be insufficient to promote notable AML differentiation. To further validate the role and druggability of CDK2 involved in AML differentiation, a suitable chemical tool is needed. Therefore, we developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK2 degradation in different cell lines without comparable degradation of other targets, and induced remarkable differentiation of AML cell lines and primary patient cells. These data clearly demonstrated the practicality and importance of PROTACs as alternative tools for verifying CDK2 protein functions.

Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.,Wang L, Shao X, Zhong T, Wu Y, Xu A, Sun X, Gao H, Liu Y, Lan T, Tong Y, Tao X, Du W, Wang W, Chen Y, Li T, Meng X, Deng H, Yang B, He Q, Ying M, Rao Y Nat Chem Biol. 2021 Mar 4. pii: 10.1038/s41589-021-00742-5. doi:, 10.1038/s41589-021-00742-5. PMID:33664520<ref>PMID:33664520</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4c13" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mur ligase|Mur ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Barreteau H]]
[[Category: Blanot D]]
[[Category: Boniface A]]
[[Category: Dementin S]]
[[Category: Dessen A]]
[[Category: Dowson CG]]
[[Category: Fulop V]]
[[Category: Gobec S]]
[[Category: Lloyd AJ]]
[[Category: Mengin-Lecreulx D]]
[[Category: Roper DI]]
[[Category: Ruane KM]]