6BFH

Structure of the kanamycin complex of aminoglycoside acetyltransferase AAC(6')-Im

Summary for 6BFH

• Entry DOI: 10.2210/pdb6bfh/pdb
• Descriptor: Aminoglycoside acetyltransferase, KANAMYCIN A, GLYCEROL, ... (4 entities in total)
• Functional Keywords: antibiotic resistance, aminoglycoside, acetyltransferase, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 22180.20

Authors

Smith, C.A.,Vakulenko, S.B. (deposition date: 2017-10-26, release date: 2017-11-08, Last modification date: 2023-10-04)

Primary citation

Smith, C.A.,Bhattacharya, M.,Toth, M.,Stewart, N.K.,Vakulenko, S.B.
Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6')-Im.
Microb Cell, 4:402-410, 2017

PubMed Abstract: Aminoglycoside 6'-acetyltransferase-Im (AAC(6')-Im) is the closest monofunctional homolog of the AAC(6')-Ie acetyltransferase of the bifunctional enzyme AAC(6')-Ie/APH(2")-Ia. The AAC(6')-Im acetyltransferase confers 4- to 64-fold higher MICs to 4,6-disubstituted aminoglycosides and the 4,5-disubstituted aminoglycoside neomycin than AAC(6')-Ie, yet unlike AAC(6')-Ie, the AAC(6')-Im enzyme does not confer resistance to the atypical aminoglycoside fortimicin. The structure of the kanamycin A complex of AAC(6')-Im shows that the substrate binds in a shallow positively-charged pocket, with the N6' amino group positioned appropriately for an efficient nucleophilic attack on an acetyl-CoA cofactor. The AAC(6')-Ie enzyme binds kanamycin A in a sufficiently different manner to position the N6' group less efficiently, thereby reducing the activity of this enzyme towards the 4,6-disubstituted aminoglycosides. Conversely, docking studies with fortimicin in both acetyltransferases suggest that the atypical aminoglycoside might bind less productively in AAC(6')-Im, thus explaining the lack of resistance to this molecule.

PubMed: 29234669
DOI: 10.15698/mic2017.12.602

Experimental method

X-RAY DIFFRACTION (1.95 Å)