Structural highlights
Publication Abstract from PubMedBroad-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 alpha-helix. This alpha-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 alpha-helix is essential to the activity of both functionalities of the full-length AAC(6')-Ie-APH(2)-Ia enzyme. Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2)-Ia revealed by crystallographic and small-angle X-ray scattering analysis.,Smith CA, Toth M, Weiss TM, Frase H, Vakulenko SB Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2754-64. doi:, 10.1107/S1399004714017635. Epub 2014 Sep 27. PMID:25286858[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
This page was last modified 07:18, 11 August 2016.