Functional dichotomy in the 16S rRNA (m1 A1408) methyltransferase family and control of catalytic activity via a novel tryptophan mediated loop reorganization

Witek, Marta A.; Conn, Graeme L.

doi:10.1093/nar/gkv1306

Functional dichotomy in the 16S rRNA (m¹ A1408) methyltransferase family and control of catalytic activity via a novel tryptophan mediated loop reorganization

Journal Article · Tue Nov 24 00:00:00 EST 2015 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkv1306· OSTI ID:1237755

Witek, Marta A. ^[1]; ^[1]

Emory Univ. School of Medicine, Atlanta, GA (United States)

Methylation of the bacterial small ribosomal subunit (16S) rRNA on the N1 position of A1408 confers exceptionally high-level resistance to a broad spectrum of aminoglycoside antibiotics. Here, we present a detailed structural and functional analysis of the Catenulisporales acidiphilia 16S rRNA (m¹A1408) methyltransferase (‘CacKam’). The apo CacKam structure closely resembles other m1A1408 methyltransferases within its conserved SAM-binding fold but the region linking core β strands 6 and 7 (the ‘β6/7 linker’) has a unique, extended structure that partially occludes the putative 16S rRNA binding surface, and sequesters the conserved and functionally critical W203 outside of the CacKam active site. Substitution of conserved residues in the SAM binding pocket reveals a functional dichotomy in the 16S rRNA (m¹A1408) methyltransferase family, with two apparently distinct molecular mechanisms coupling cosubstrate/ substrate binding to catalytic activity. Our results additionally suggest that CacKam exploits the W203-mediated remodeling of the β6/7 linker as a novel mechanism to control 30S substrate recognition and enzymatic turnover.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health-National Inst. of Allergy and Infectious Diseases; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1237755

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 1 Vol. 44; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (50)

Interaction of kanamycin and related antibiotics with the large subunit of ribosomes and the inhibition of translocation Misumi, Masarou; Nishimura, Toshio; Komai, Tomoyoshi Biochemical and Biophysical Research Communications, Vol. 84, Issue 2 https://doi.org/10.1016/0006-291x(78)90178-x	journal	September 1978
Inhibition of ribosomal translocation by aminoglycoside antibiotics Jesús Cabañas, María; Vázquez, David; Modolell, Juan Biochemical and Biophysical Research Communications, Vol. 83, Issue 3 https://doi.org/10.1016/0006-291x(78)91493-6	journal	August 1978
Rapid chemical probing of conformation in 16 S ribosomal RNA and 30 S ribosomal subunits using primer extension Moazed, Danesh; Stern, Seth; Noller, Harry F. Journal of Molecular Biology, Vol. 187, Issue 3 https://doi.org/10.1016/0022-2836(86)90441-9	journal	February 1986
Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides Beauclerk, Alan A. D.; Cundliffe, Eric Journal of Molecular Biology, Vol. 193, Issue 4 https://doi.org/10.1016/0022-2836(87)90349-4	journal	February 1987
Expansion of the aminoglycoside-resistance 16S rRNA (m1A1408) methyltransferase family: Expression and functional characterization of four hypothetical enzymes of diverse bacterial origin Witek, Marta A.; Conn, Graeme L. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1844, Issue 9 https://doi.org/10.1016/j.bbapap.2014.06.012	journal	September 2014
Control of Catalytic Cycle by a Pair of Analogous tRNA Modification Enzymes Christian, Thomas; Lahoud, Georges; Liu, Cuiping Journal of Molecular Biology, Vol. 400, Issue 2 https://doi.org/10.1016/j.jmb.2010.05.003	journal	July 2010
A role for flexible loops in enzyme catalysis Malabanan, M. Merced; Amyes, Tina L.; Richard, John P. Current Opinion in Structural Biology, Vol. 20, Issue 6 https://doi.org/10.1016/j.sbi.2010.09.005	journal	December 2010
SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold Martin, J. Current Opinion in Structural Biology, Vol. 12, Issue 6 https://doi.org/10.1016/s0959-440x(02)00391-3	journal	December 2002
Many paths to methyltransfer: a chronicle of convergence Schubert, Heidi L.; Blumenthal, Robert M.; Cheng, Xiaodong Trends in Biochemical Sciences, Vol. 28, Issue 6 https://doi.org/10.1016/s0968-0004(03)00090-2	journal	June 2003
Molecular Insights into Aminoglycoside Action and Resistance Magnet, Sophie; Blanchard, John S. Chemical Reviews, Vol. 105, Issue 2 https://doi.org/10.1021/cr0301088	journal	February 2005
The bacterial ribosome as a target for antibiotics Poehlsgaard, Jacob; Douthwaite, Stephen Nature Reviews Microbiology, Vol. 3, Issue 11 https://doi.org/10.1038/nrmicro1265	journal	October 2005
Ribosome-targeting antibiotics and mechanisms of bacterial resistance Wilson, Daniel N. Nature Reviews Microbiology, Vol. 12, Issue 1 https://doi.org/10.1038/nrmicro3155	journal	December 2013
Protein conformational dynamics in the mechanism of HIV-1 protease catalysis Torbeev, V. Y.; Raghuraman, H.; Hamelberg, D. Proceedings of the National Academy of Sciences, Vol. 108, Issue 52 https://doi.org/10.1073/pnas.1111202108	journal	December 2011
Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA Dunkle, J. A.; Vinal, K.; Desai, P. M. Proceedings of the National Academy of Sciences, Vol. 111, Issue 17 https://doi.org/10.1073/pnas.1402789111	journal	April 2014
Cation-pi interactions in structural biology Gallivan, J. P.; Dougherty, D. A. Proceedings of the National Academy of Sciences, Vol. 96, Issue 17 https://doi.org/10.1073/pnas.96.17.9459	journal	August 1999
Clustal W and Clustal X version 2.0 Larkin, M. A.; Blackshields, G.; Brown, N. P. Bioinformatics, Vol. 23, Issue 21, p. 2947-2948 https://doi.org/10.1093/bioinformatics/btm404	journal	September 2007
Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit Husain, Nilofer; Obranić, Sonja; Koscinski, Lukasz Nucleic Acids Research, Vol. 39, Issue 5 https://doi.org/10.1093/nar/gkq1033	journal	November 2010
Aminoglycosides: how should we use them in the 21st century? Jackson, Justin; Chen, Caroline; Buising, Kirsty Current Opinion in Infectious Diseases, Vol. 26, Issue 6 https://doi.org/10.1097/qco.0000000000000012	journal	January 2013
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion Painter, Jay; Merritt, Ethan A. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 4 https://doi.org/10.1107/s0907444906005270	journal	March 2006
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/s0907444910007493	journal	March 2010
PDB_REDO : constructive validation, more than just looking for errors Joosten, Robbie P.; Joosten, Krista; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/s0907444911054515	journal	March 2012
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/s0907444996012255	journal	May 1997
30S Subunit-Dependent Activation of the Sorangium cellulosum So ce56 Aminoglycoside Resistance-Conferring 16S rRNA Methyltransferase Kmr Savic, Miloje; Sunita, S.; Zelinskaya, Natalia Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 5 https://doi.org/10.1128/aac.00056-15	journal	March 2015
Novel Plasmid-Mediated 16S rRNA m1A1408 Methyltransferase, NpmA, Found in a Clinically Isolated Escherichia coli Strain Resistant to Structurally Diverse Aminoglycosides Wachino, J. -i.; Shibayama, K.; Kurokawa, H. Antimicrobial Agents and Chemotherapy, Vol. 51, Issue 12 https://doi.org/10.1128/aac.00926-07	journal	September 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Molecular and Enzymatic Profiles of Mammalian DNA Methyltransferases: Structures and Targets for Drugs Xu, F.; Mao, C.; Ding, Y. Current Medicinal Chemistry, Vol. 17, Issue 33 https://doi.org/10.2174/092986710793205372	journal	November 2012
A functional role for a flexible loop containing Glu182 in the class II fructose-1,6-bisphosphate aldolase from Escherichia coli 1 1Edited by D. Rees Zgiby, S.; Plater, A. R.; Bates, M. A. Journal of Molecular Biology, Vol. 315, Issue 2 https://doi.org/10.1006/jmbi.2001.5237	journal	January 2002
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Interaction of kanamycin and related antibiotics with the large subunit of ribosomes and the inhibition of translocation Misumi, Masarou; Nishimura, Toshio; Komai, Tomoyoshi Biochemical and Biophysical Research Communications, Vol. 84, Issue 2 https://doi.org/10.1016/0006-291X(78)90178-X	journal	September 1978
Inhibition of ribosomal translocation by aminoglycoside antibiotics Jesús Cabañas, María; Vázquez, David; Modolell, Juan Biochemical and Biophysical Research Communications, Vol. 83, Issue 3 https://doi.org/10.1016/0006-291X(78)91493-6	journal	August 1978
Structure and Function of Lipases Derewenda, Zygmunt S. Lipoproteins, Apolipoproteins, and Lipases https://doi.org/10.1016/S0065-3233(08)60637-3	book	January 1994
The Conformational Plasticity of Protein Kinases Huse, Morgan; Kuriyan, John Cell, Vol. 109, Issue 3 https://doi.org/10.1016/S0092-8674(02)00741-9	journal	May 2002
SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold Martin, J. Current Opinion in Structural Biology, Vol. 12, Issue 6 https://doi.org/10.1016/S0959-440X(02)00391-3	journal	December 2002
Many paths to methyltransfer: a chronicle of convergence Schubert, Heidi L.; Blumenthal, Robert M.; Cheng, Xiaodong Trends in Biochemical Sciences, Vol. 28, Issue 6 https://doi.org/10.1016/S0968-0004(03)00090-2	journal	June 2003
Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: An update Wachino, Jun-ichi; Arakawa, Yoshichika Drug Resistance Updates, Vol. 15, Issue 3 https://doi.org/10.1016/j.drup.2012.05.001	journal	June 2012
Cation−π Interactions in Proteins: Can Simple Models Provide an Accurate Description? Minoux, Hervé; Chipot, Christophe Journal of the American Chemical Society, Vol. 121, Issue 44 https://doi.org/10.1021/ja990914p	journal	November 1999
Flexibility and function in HIV-1 protease Nicholson, Linda K.; Yamazaki, Toshimasa; Torchia, Dennis A. Nature Structural & Molecular Biology, Vol. 2, Issue 4 https://doi.org/10.1038/nsb0495-274	journal	April 1995
POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level Cavallo, L. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg601	journal	July 2003
Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics Savic, M.; Lovric, J.; Tomic, T. I. Nucleic Acids Research, Vol. 37, Issue 16 https://doi.org/10.1093/nar/gkp575	journal	July 2009
Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria Macmaster, Rachel; Zelinskaya, Natalia; Savic, Miloje Nucleic Acids Research, Vol. 38, Issue 21 https://doi.org/10.1093/nar/gkq627	journal	July 2010
Aminoglycosides: how should we use them in the 21st century? Jackson, Justin; Chen, Caroline; Buising, Kirsty Current Opinion in Infectious Diseases, Vol. 26, Issue 6 https://doi.org/10.1097/QCO.0000000000000012	journal	January 2013
WebLogo: A Sequence Logo Generator Crooks, Gavin E.; Hon, Gary; Chandonia, John-Marc Genome Research, Vol. 14, Issue 6, p. 1188-1190 https://doi.org/10.1101/gr.849004	journal	May 2004
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion Painter, Jay; Merritt, Ethan A. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 4 https://doi.org/10.1107/S0907444906005270	journal	March 2006
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
PDB_REDO : constructive validation, more than just looking for errors Joosten, Robbie P.; Joosten, Krista; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444911054515	journal	March 2012
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
30S Subunit-Dependent Activation of the Sorangium cellulosum So ce56 Aminoglycoside Resistance-Conferring 16S rRNA Methyltransferase Kmr Savic, Miloje; Sunita, S.; Zelinskaya, Natalia Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 5 https://doi.org/10.1128/AAC.00056-15	journal	March 2015
Novel Plasmid-Mediated 16S rRNA m1A1408 Methyltransferase, NpmA, Found in a Clinically Isolated Escherichia coli Strain Resistant to Structurally Diverse Aminoglycosides Wachino, J. -i.; Shibayama, K.; Kurokawa, H. Antimicrobial Agents and Chemotherapy, Vol. 51, Issue 12 https://doi.org/10.1128/AAC.00926-07	journal	September 2007

Cited By (2)

The structure and function of Mycobacterium tuberculosis MazF-mt6 toxin provide insights into conserved features of MazF endonucleases Hoffer, Eric D.; Miles, Stacey J.; Dunham, Christine M. Journal of Biological Chemistry, Vol. 292, Issue 19 https://doi.org/10.1074/jbc.m117.779306	journal	March 2017
Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition Nosrati, Meisam; Dey, Debayan; Mehrani, Atousa Journal of Biological Chemistry, Vol. 294, Issue 46 https://doi.org/10.1074/jbc.ra119.011181	journal	October 2019

Similar Records

Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition

Journal Article · Mon Oct 07 20:00:00 EDT 2019 · Journal of Biological Chemistry · OSTI ID:1577157

Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit

Journal Article · Mon Nov 08 19:00:00 EST 2010 · Nucleic Acids Research · OSTI ID:1625471

Structural Basis for the Methylation of G1405 in 16S rRNA by Aminoglycoside Resistance Methyltransferase Sgm from an Antibiotic Producer: a Diversity of Active Sites in m7G Methyltransferases

Journal Article · Thu Dec 31 23:00:00 EST 2009 · Nucleic Acids Research · OSTI ID:1019972

Related Subjects

59 BASIC BIOLOGICAL SCIENCES