6vot

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Crystal structure of Pseudomonas aerugonisa PBP3 complexed to gamma-lactam YU253434

Structural highlights

6vot is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FTSI_PSEAE Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]^[1]

Publication Abstract from PubMed

Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel gamma-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of gamma-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of beta-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.

A gamma-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli.,Goldberg JA, Nguyen H, Kumar V, Spencer EJ, Hoyer D, Marshall EK, Cmolik A, O'Shea M, Marshall SH, Hujer AM, Hujer KM, Rudin SD, Domitrovic TN, Bethel CR, Papp-Wallace KM, Logan LK, Perez F, Jacobs MR, van Duin D, Kreiswirth BM, Bonomo RA, Plummer MS, van den Akker F J Med Chem. 2020 Jun 11;63(11):5990-6002. doi: 10.1021/acs.jmedchem.0c00255. Epub, 2020 Jun 2. PMID:32420736^[2]

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

References

↑ de Leon SR, Daniels K, Clarke AJ. Production and purification of the penicillin-binding protein 3 from Pseudomonas aeruginosa. Protein Expr Purif. 2010 Oct;73(2):177-83. doi: 10.1016/j.pep.2010.05.005. Epub, 2010 May 16. PMID:20580675 doi:http://dx.doi.org/10.1016/j.pep.2010.05.005
↑ Goldberg JA, Nguyen H, Kumar V, Spencer EJ, Hoyer D, Marshall EK, Cmolik A, O'Shea M, Marshall SH, Hujer AM, Hujer KM, Rudin SD, Domitrovic TN, Bethel CR, Papp-Wallace KM, Logan LK, Perez F, Jacobs MR, van Duin D, Kreiswirth BM, Bonomo RA, Plummer MS, van den Akker F. A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli. J Med Chem. 2020 Jun 11;63(11):5990-6002. PMID:32420736 doi:10.1021/acs.jmedchem.0c00255