4QC6

Crystal structure of aminoglycoside 6'-acetyltransferase-Ie

Summary for 4QC6

• Entry DOI: 10.2210/pdb4qc6/pdb
• Descriptor: Bifunctional AAC/APH, KANAMYCIN A, (3R,5S,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3,5-diphosphaheptadecane-17-sulfinic acid 3,5-dioxide (non-preferred name), ... (5 entities in total)
• Functional Keywords: antibiotic resistance, gnat family, acetyltransferase, acetylcoenzyme-a, aminoglycoside, transferase, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Staphylococcus warneri
• Cellular location: Cytoplasm : Q7ATH7
• Total number of polymer chains: 2
• Total formula weight: 46269.62

Authors

Smith, C.A.,Toth, M.,Weiss, T.M.,Frase, H.,Vakulenko, S.B. (deposition date: 2014-05-09, release date: 2014-10-22, Last modification date: 2024-02-28)

Primary citation

Smith, C.A.,Toth, M.,Weiss, T.M.,Frase, H.,Vakulenko, S.B.
Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia revealed by crystallographic and small-angle X-ray scattering analysis.
Acta Crystallogr.,Sect.D, 70:2754-2764, 2014

PubMed Abstract: Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6')-Ie-APH(2'')-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6')-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2'')-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2'')-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6')-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6')-Ie enzyme is joined to APH(2'')-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2'')-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6')-Ie-APH(2'')-Ia enzyme.

PubMed: 25286858
DOI: 10.1107/S1399004714017635

Experimental method

X-RAY DIFFRACTION (1.3 Å)