9w7p

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Crystal Structure of Ledaborbactam in complex with SME-1 class A Carbapenemase

Structural highlights

9w7p is a 2 chain structure with sequence from Serratia marcescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLAS1_SERMA Class A beta-lactamase which confers resistance to the beta-lactam antibiotics, including penicillins, some cephalosporins and carbapenems, to JM109 strain E.coli (PubMed:11807251, PubMed:8092824). Acts via hydrolysis of the beta-lactam ring (PubMed:11036019, PubMed:8092824). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities (PubMed:11036019).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Bicyclic boronic acids inhibit SME-1 carbapenemase via a unique pi-pi stacking with His105 and covalent interaction with Ser70. Ledaborbactam shows the strongest inhibition, with the lowest k(i) and enhanced structural stability. X-ray crystallography and molecular dynamics reveal key features helpful in structure-based optimization of boronates targeting class A beta-lactamases.

Beyond structure and activity: targeting class A carbapenemases with monocyclic and bicyclic boronic acids to counter antimicrobial resistance.,Dhankhar K, Hazra M, Nair ASR, Alhmeidi Alkhatib AE, Mishra NC, Hazra S Org Biomol Chem. 2025 Nov 11. doi: 10.1039/d5ob01703c. PMID:41217385^[4]

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

References

↑ Queenan AM, Torres-Viera C, Gold HS, Carmeli Y, Eliopoulos GM, Moellering RC Jr, Quinn JP, Hindler J, Medeiros AA, Bush K. SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains. Antimicrob Agents Chemother. 2000 Nov;44(11):3035-9. PMID:11036019 doi:10.1128/AAC.44.11.3035-3039.2000
↑ Sougakoff W, L'Hermite G, Pernot L, Naas T, Guillet V, Nordmann P, Jarlier V, Delettre J. Structure of the imipenem-hydrolyzing class A beta-lactamase SME-1 from Serratia marcescens. Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):267-74. Epub 2002, Jan 24. PMID:11807251
↑ Naas T, Vandel L, Sougakoff W, Livermore DM, Nordmann P. Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6. Antimicrob Agents Chemother. 1994 Jun;38(6):1262-70. PMID:8092824 doi:10.1128/AAC.38.6.1262
↑ Dhankhar K, Hazra M, Nair ASR, Alhmeidi Alkhatib AE, Mishra NC, Hazra S. Beyond structure and activity: targeting class A carbapenemases with monocyclic and bicyclic boronic acids to counter antimicrobial resistance. Org Biomol Chem. 2025 Nov 11. PMID:41217385 doi:10.1039/d5ob01703c