ArticleThe Journal of biological chemistry2011
Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
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- Aminoglycoside-Modifying Enzymes Are Sufficient to MakeAntibiotics (Basel, Switzerland) · 2022Article
- The Novel Serine/Threonine Protein Kinase LmjF.22.0810 fromBiomolecules · 2019Article
- Structural basis for the substrate recognition of aminoglycoside 7''-phosphotransferase-Ia from Streptomyces hygroscopicus.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Potential for reduction of streptogramin A resistance revealed by structural analysis of acetyltransferase VatA.Antimicrobial agents and chemotherapy · 2014Article
- Resilience of biochemical activity in protein domains in the face of structural divergence.Current opinion in structural biology · 2014Review
- Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance.The Biochemical journal · 2013Article
- Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections.Future medicinal chemistry · 2013Review
- Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance.Frontiers in cellular and infection microbiology · 2013Review
- Aminoglycoside 2''-phosphotransferase IIIa (APH(2'')-IIIa) prefers GTP over ATP: structural templates for nucleotide recognition in the bacterial aminoglycoside-2'' kinases.The Journal of biological chemistry · 2012Article
- Effects of altering aminoglycoside structures on bacterial resistance enzyme activities.Antimicrobial agents and chemotherapy · 2011Article
- An intein with genetically selectable markers provides a new approach to internally label proteins with GFP.BMC biotechnology · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes responsible for bacterial resistance to the atypical aminoglycoside antibiotic hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in complex with hygB at 1.95 Å resolution. The APH(4)-Ia structure adapts a general two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with the active site located at the interdomain cavity. The enzyme forms an extended hydrogen bond network with hygB primarily through polar and acidic side chain groups. Individual alanine substitutions of seven residues involved in hygB binding did not have significant effect on APH(4)-Ia enzymatic activity, indicating that the binding affinity is spread across a distributed network. hygB appeared as the only substrate recognized by APH(4)-Ia among the panel of 14 aminoglycoside compounds. Analysis of the active site architecture and the interaction with the hygB molecule demonstrated several unique features supporting such restricted substrate specificity. Primarily the APH(4)-Ia substrate-binding site contains a cluster of hydrophobic residues that provides a complementary surface to the twisted structure of the substrate. Similar to APH(2″) enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for phosphoryl transfer. The defined structural features of APH(4)-Ia interactions with hygB and the promiscuity in regard to ATP or GTP binding could be exploited for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme.
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