6N80

S. aureus ClpP bound to anti-4a

Summary for 6N80

• Entry DOI: 10.2210/pdb6n80/pdb
• Descriptor: ATP-dependent Clp protease proteolytic subunit, N-[(1R)-1-borono-3-methylbutyl]-N~2~-(2-chloro-4-methoxybenzene-1-carbonyl)-L-leucinamide (3 entities in total)
• Functional Keywords: clpp, hydrolase
• Biological source: Staphylococcus aureus (strain NCTC 8325)
• Total number of polymer chains: 14
• Total formula weight: 322285.63

Authors

Lee, R.E.,Griffith, E.C. (deposition date: 2018-11-28, release date: 2019-06-26, Last modification date: 2024-10-23)

Primary citation

Tan, J.,Grouleff, J.J.,Jitkova, Y.,Diaz, D.B.,Griffith, E.C.,Shao, W.,Bogdanchikova, A.F.,Poda, G.,Schimmer, A.D.,Lee, R.E.,Yudin, A.K.
De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX.
J.Med.Chem., 62:6377-6390, 2019

PubMed Abstract: Boronic acids have attracted the attention of synthetic and medicinal chemists due to boron's ability to modulate enzyme function. Recently, we demonstrated that boron-containing amphoteric building blocks facilitate the discovery of bioactive aminoboronic acids. Herein, we have augmented this capability with a de novo library design and a virtual screening platform modified for covalent ligands. This technique has allowed us to rapidly design and identify a series of α-aminoboronic acids as the first inhibitors of human ClpXP, which is responsible for the degradation of misfolded proteins.

PubMed: 31187989
DOI: 10.1021/acs.jmedchem.9b00878

Experimental method

X-RAY DIFFRACTION (1.96 Å)