4c13

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x-ray crystal structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lysx-ray crystal structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lys

Structural highlights

4c13 is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3]

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[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ ITO E, STROMINGER JL. ENZYMATIC SYNTHESIS OF THE PEPTIDE IN BACTERIAL URIDINE NUCLEOTIDES. III. PURIFICATION AND PROPERTIES OF L-LYSIN-ADDING ENZYME. J Biol Chem. 1964 Jan;239:210-4. PMID:14114846
  2. ↑ Mengin-Lecreulx D, Falla T, Blanot D, van Heijenoort J, Adams DJ, Chopra I. Expression of the Staphylococcus aureus UDP-N-acetylmuramoyl- L-alanyl-D-glutamate:L-lysine ligase in Escherichia coli and effects on peptidoglycan biosynthesis and cell growth. J Bacteriol. 1999 Oct;181(19):5909-14. PMID:10498701
  3. ↑ Gardete S, Ludovice AM, Sobral RG, Filipe SR, de Lencastre H, Tomasz A. Role of murE in the Expression of beta-lactam antibiotic resistance in Staphylococcus aureus. J Bacteriol. 2004 Mar;186(6):1705-13. PMID:14996801
  4. ↑ 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. Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy. Nat Chem Biol. 2021 Mar 4. pii: 10.1038/s41589-021-00742-5. doi:, 10.1038/s41589-021-00742-5. PMID:33664520 doi:http://dx.doi.org/10.1038/s41589-021-00742-5

4c13, resolution 1.90Å

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