Structure of an Enzyme Required for Aminoglycoside Antibiotic Resistance Reveals Homology to Eukaryotic Protein Kinases
Bacterial resistance to aminoglycoside antibiotics is almost exclusively accomplished through either phosphorylation, adenylylation, or acetylation of the antibacterial agent. The aminoglycoside kinase, APH(3′)-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. Th...
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Veröffentlicht in: | Cell 1997-06, Vol.89 (6), p.887-895 |
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description | Bacterial resistance to aminoglycoside antibiotics is almost exclusively accomplished through either phosphorylation, adenylylation, or acetylation of the antibacterial agent. The aminoglycoside kinase, APH(3′)-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. The crystal structure of this enzyme complexed with ADP was determined at 2.2 Å resolution. The three-dimensional fold of APH(3′)-IIIa reveals a striking similarity to eukaryotic protein kinases despite a virtually complete lack of sequence homology. Nearly half of the APH(3′)-IIIa sequence adopts a conformation identical to that seen in these kinases. Substantial differences are found in the location and conformation of residues presumably responsible for second-substrate specificity. These results indicate that APH(3′) enzymes and eukaryotic-type protein kinases share a common ancestor. |
doi_str_mv | 10.1016/S0092-8674(00)80274-3 |
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The aminoglycoside kinase, APH(3′)-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. The crystal structure of this enzyme complexed with ADP was determined at 2.2 Å resolution. The three-dimensional fold of APH(3′)-IIIa reveals a striking similarity to eukaryotic protein kinases despite a virtually complete lack of sequence homology. Nearly half of the APH(3′)-IIIa sequence adopts a conformation identical to that seen in these kinases. Substantial differences are found in the location and conformation of residues presumably responsible for second-substrate specificity. 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The aminoglycoside kinase, APH(3′)-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. The crystal structure of this enzyme complexed with ADP was determined at 2.2 Å resolution. The three-dimensional fold of APH(3′)-IIIa reveals a striking similarity to eukaryotic protein kinases despite a virtually complete lack of sequence homology. Nearly half of the APH(3′)-IIIa sequence adopts a conformation identical to that seen in these kinases. Substantial differences are found in the location and conformation of residues presumably responsible for second-substrate specificity. These results indicate that APH(3′) enzymes and eukaryotic-type protein kinases share a common ancestor.</description><subject>Aminoglycosides</subject><subject>Anti-Bacterial Agents</subject><subject>Binding Sites - physiology</subject><subject>Crystallography</subject><subject>Drug Resistance, Microbial</subject><subject>Enterococcus - chemistry</subject><subject>Enterococcus - enzymology</subject><subject>Enterococcus - genetics</subject><subject>Eukaryotic Cells - enzymology</subject><subject>Kanamycin Kinase</subject><subject>Molecular Sequence Data</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - chemistry</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - genetics</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - metabolism</subject><subject>Protein Kinases - chemistry</subject><subject>Protein Kinases - genetics</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Sequence Homology, Amino Acid</subject><subject>Signal Transduction - physiology</subject><subject>Staphylococcus - chemistry</subject><subject>Staphylococcus - enzymology</subject><subject>Staphylococcus - genetics</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQhi1EBVvan4DkE4JD2nESx84JrdAWqiK1Ku3ZSuwxMiQx2A7V9tfj_RBXTj7M887I70PIKYMvDFjz9Q6gLQvZiPoc4EJCKeqiOiALBq0oaibKQ7J4Q47JxxgfAEByzo_IUVsCNCAW5N9dCrNOc0DqLe0mupr-r0ekv_F5dgENtT7Q5egmfz-stY_OIF1OyfXOJ6czFl1M3aQ3iRfshkhv_OgHf7-mydPV_NiF9Zb8FXxCN9Efbuoixk_kg800ft6_J-Tvt9Wfq5vi9uf196vlbaE5b1IhDMiqQ92ClKJGA9ggK7m2jHEjkPdVL8rKGGta2zMtrWa10ZbLTgLvoa9OyNlu71PwzzPGpEYXNQ5DN6GfoxItCJk3vguyphRl02xAvgN18DEGtOopuDF_UzFQGzNqa0ZtalcAamtGVTl3uj8w9yOat9ReRZ5f7uaY63hxGFTUDnOzJnvQSRnv3rnwCl15oEY</recordid><startdate>19970613</startdate><enddate>19970613</enddate><creator>Hon, Wai-Ching</creator><creator>McKay, Geoffrey A.</creator><creator>Thompson, Paul R.</creator><creator>Sweet, Robert M.</creator><creator>Yang, Daniel S.C.</creator><creator>Wright, Gerard D.</creator><creator>Berghuis, Albert M.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>19970613</creationdate><title>Structure of an Enzyme Required for Aminoglycoside Antibiotic Resistance Reveals Homology to Eukaryotic Protein Kinases</title><author>Hon, Wai-Ching ; McKay, Geoffrey A. ; Thompson, Paul R. ; Sweet, Robert M. ; Yang, Daniel S.C. ; Wright, Gerard D. ; Berghuis, Albert M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-7d083aec908874ed0e6e125cf115d7e5b3b723ddfd9fb1c8fc14dcf58a805b0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Aminoglycosides</topic><topic>Anti-Bacterial Agents</topic><topic>Binding Sites - physiology</topic><topic>Crystallography</topic><topic>Drug Resistance, Microbial</topic><topic>Enterococcus - chemistry</topic><topic>Enterococcus - enzymology</topic><topic>Enterococcus - genetics</topic><topic>Eukaryotic Cells - enzymology</topic><topic>Kanamycin Kinase</topic><topic>Molecular Sequence Data</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - chemistry</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - genetics</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - metabolism</topic><topic>Protein Kinases - chemistry</topic><topic>Protein Kinases - genetics</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Sequence Homology, Amino Acid</topic><topic>Signal Transduction - physiology</topic><topic>Staphylococcus - chemistry</topic><topic>Staphylococcus - enzymology</topic><topic>Staphylococcus - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hon, Wai-Ching</creatorcontrib><creatorcontrib>McKay, Geoffrey A.</creatorcontrib><creatorcontrib>Thompson, Paul R.</creatorcontrib><creatorcontrib>Sweet, Robert M.</creatorcontrib><creatorcontrib>Yang, Daniel S.C.</creatorcontrib><creatorcontrib>Wright, Gerard D.</creatorcontrib><creatorcontrib>Berghuis, Albert M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hon, Wai-Ching</au><au>McKay, Geoffrey A.</au><au>Thompson, Paul R.</au><au>Sweet, Robert M.</au><au>Yang, Daniel S.C.</au><au>Wright, Gerard D.</au><au>Berghuis, Albert M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure of an Enzyme Required for Aminoglycoside Antibiotic Resistance Reveals Homology to Eukaryotic Protein Kinases</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>1997-06-13</date><risdate>1997</risdate><volume>89</volume><issue>6</issue><spage>887</spage><epage>895</epage><pages>887-895</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Bacterial resistance to aminoglycoside antibiotics is almost exclusively accomplished through either phosphorylation, adenylylation, or acetylation of the antibacterial agent. The aminoglycoside kinase, APH(3′)-IIIa, catalyzes the phosphorylation of a broad spectrum of aminoglycoside antibiotics. The crystal structure of this enzyme complexed with ADP was determined at 2.2 Å resolution. The three-dimensional fold of APH(3′)-IIIa reveals a striking similarity to eukaryotic protein kinases despite a virtually complete lack of sequence homology. Nearly half of the APH(3′)-IIIa sequence adopts a conformation identical to that seen in these kinases. Substantial differences are found in the location and conformation of residues presumably responsible for second-substrate specificity. These results indicate that APH(3′) enzymes and eukaryotic-type protein kinases share a common ancestor.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9200607</pmid><doi>10.1016/S0092-8674(00)80274-3</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aminoglycosides Anti-Bacterial Agents Binding Sites - physiology Crystallography Drug Resistance, Microbial Enterococcus - chemistry Enterococcus - enzymology Enterococcus - genetics Eukaryotic Cells - enzymology Kanamycin Kinase Molecular Sequence Data Phosphotransferases (Alcohol Group Acceptor) - chemistry Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - metabolism Protein Kinases - chemistry Protein Kinases - genetics Protein Structure, Secondary Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction - physiology Staphylococcus - chemistry Staphylococcus - enzymology Staphylococcus - genetics |
title | Structure of an Enzyme Required for Aminoglycoside Antibiotic Resistance Reveals Homology to Eukaryotic Protein Kinases |
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