Genomes and Genes
Summary: Acyltransferases that use AMINO ACYL TRNA as the amino acid donor in formation of a peptide bond. There are ribosomal and non-ribosomal peptidyltransferases.
- Popham D, Young K. Role of penicillin-binding proteins in bacterial cell morphogenesis. Curr Opin Microbiol. 2003;6:594-9 pubmed..In addition, the low molecular weight PBPs, by varying the substrates on which other PBPs act, alter peptidoglycan synthesis or turnover, with profound effects on morphology. ..
- Steitz T. On the structural basis of peptide-bond formation and antibiotic resistance from atomic structures of the large ribosomal subunit. FEBS Lett. 2005;579:955-8 pubmed..The structure shows that the ribosome is indeed a ribozyme. ..
- Weinger J, Parnell K, Dorner S, Green R, Strobel S. Substrate-assisted catalysis of peptide bond formation by the ribosome. Nat Struct Mol Biol. 2004;11:1101-6 pubmed..These results suggest that substrate assistance has been retained as a catalytic strategy during the evolution of the prebiotic peptidyl transferase center into the modern ribosome. ..
- Costa T, Priyadarshini R, Jacobs Wagner C. Localization of PBP3 in Caulobacter crescentus is highly dynamic and largely relies on its functional transpeptidase domain. Mol Microbiol. 2008;70:634-51 pubmed publisher..Collectively, our results suggest a role for PBP3 in pole morphogenesis and provide new insights into the process of peptidoglycan assembly during division...
- Wei Y, McPherson D, Popham D. A mother cell-specific class B penicillin-binding protein, PBP4b, in Bacillus subtilis. J Bacteriol. 2004;186:258-61 pubmed..Loss of PBP4b, alone and in combination with other sporulation-specific PBPs, had no effect on spore peptidoglycan structure. ..
- Schuwirth B, Borovinskaya M, Hau C, Zhang W, Vila Sanjurjo A, Holton J, et al. Structures of the bacterial ribosome at 3.5 A resolution. Science. 2005;310:827-34 pubmed
- Brunelle J, Youngman E, Sharma D, Green R. The interaction between C75 of tRNA and the A loop of the ribosome stimulates peptidyl transferase activity. RNA. 2006;12:33-9 pubmed
- Varma A, Young K. FtsZ collaborates with penicillin binding proteins to generate bacterial cell shape in Escherichia coli. J Bacteriol. 2004;186:6768-74 pubmed
- Maden B. Historical review: Peptidyl transfer, the Monro era. Trends Biochem Sci. 2003;28:619-24 pubmed..Monro's 'fragment reaction', the ribosome catalyzed reaction of a fragment of formylmethionyl-tRNA with puromycin, remains in use in work on peptidyl transfer. ..
- Baxter Roshek J, Petrov A, Dinman J. Optimization of ribosome structure and function by rRNA base modification. PLoS ONE. 2007;2:e174 pubmed..These findings represent a direct demonstration in support of the prevailing hypothesis that rRNA modifications serve to optimize rRNA structure for production of accurate and efficient ribosomes. ..
- Triboulet S, Dubée V, Lecoq L, Bougault C, Mainardi J, Rice L, et al. Kinetic features of L,D-transpeptidase inactivation critical for ?-lactam antibacterial activity. PLoS ONE. 2013;8:e67831 pubmed publisher..These results pave the way for optimization of the ?-lactam scaffold for L,D-transpeptidase-inactivation. ..
- Hesslein A, Katunin V, Beringer M, Kosek A, Rodnina M, Strobel S. Exploration of the conserved A+C wobble pair within the ribosomal peptidyl transferase center using affinity purified mutant ribosomes. Nucleic Acids Res. 2004;32:3760-70 pubmed
- Brodersen D, Nissen P. The social life of ribosomal proteins. FEBS J. 2005;272:2098-108 pubmed..In this review we highlight some of the many known and important functions of ribosomal proteins, both during translation on the ribosome and in a wider context. ..
- Mainardi J, Fourgeaud M, Hugonnet J, Dubost L, Brouard J, Ouazzani J, et al. A novel peptidoglycan cross-linking enzyme for a beta-lactam-resistant transpeptidation pathway. J Biol Chem. 2005;280:38146-52 pubmed..Ldt(fm) homologues are encountered sporadically among taxonomically distant bacteria, indicating that ld-transpeptidase-mediated resistance may emerge in various pathogens. ..
- Rakauskaite R, Dinman J. Mutations of highly conserved bases in the peptidyltransferase center induce compensatory rearrangements in yeast ribosomes. RNA. 2011;17:855-64 pubmed publisher..the proto-ribosome area). We suggest that a certain degree of structural plasticity is built into the ribosome, enabling it to ensure accurate translation of the genetic code while providing it with the flexibility to adapt and evolve. ..
- Voorhees R, Weixlbaumer A, Loakes D, Kelley A, Ramakrishnan V. Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosome. Nat Struct Mol Biol. 2009;16:528-33 pubmed publisher..They also reveal interactions between the ribosomal proteins L16 and L27 and the tRNA substrates, helping to elucidate the role of these proteins in peptidyl transfer. ..
- Seidelt B, Innis C, Wilson D, Gartmann M, Armache J, Villa E, et al. Structural insight into nascent polypeptide chain-mediated translational stalling. Science. 2009;326:1412-5 pubmed publisher..We propose a model whereby interactions within the tunnel are relayed to the peptidyltransferase center to inhibit translation. Moreover, we show that nascent chains adopt distinct conformations within the ribosomal exit tunnel. ..
- Meskauskas A, Baxter J, Carr E, Yasenchak J, Gallagher J, Baserga S, et al. Delayed rRNA processing results in significant ribosome biogenesis and functional defects. Mol Cell Biol. 2003;23:1602-13 pubmed..The frameshifting defect is accentuated when the demand for ribosomes is highest, suggesting that rRNA posttranscriptional modification is the bottleneck in ribosome biogenesis. ..
- Pinho M, Errington J. Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates. Mol Microbiol. 2005;55:799-807 pubmed..In methicillin-resistant S. aureus, addition of oxacillin does not result in delocalization of PBP2 indicating that acylated PBP2 can be maintained in place by functional PBP2A, the central element of this resistance mechanism. ..
- Vazquez Laslop N, Thum C, Mankin A. Molecular mechanism of drug-dependent ribosome stalling. Mol Cell. 2008;30:190-202 pubmed publisher..The cladinose-containing macrolide antibiotic in the tunnel positions the nascent peptide for interaction with the tunnel sensory elements. ..
- Arbeloa A, Segal H, Hugonnet J, Josseaume N, Dubost L, Brouard J, et al. Role of class A penicillin-binding proteins in PBP5-mediated beta-lactam resistance in Enterococcus faecalis. J Bacteriol. 2004;186:1221-8 pubmed..The latter enzyme was not inhibited by moenomycin, since deletion of the three class A PBP genes led to high-level resistance to this glycosyltransferase inhibitor. ..
- Xaplanteri M, Petropoulos A, Dinos G, Kalpaxis D. Localization of spermine binding sites in 23S rRNA by photoaffinity labeling: parsing the spermine contribution to ribosomal 50S subunit functions. Nucleic Acids Res. 2005;33:2792-805 pubmed..However, they exhibited higher reactivity toward puromycin and enhanced tRNA-translocation efficiency. These results suggest an essential role for polyamines in the structural and functional integrity of the large ribosomal subunit. ..
- Fulle S, Gohlke H. Statics of the ribosomal exit tunnel: implications for cotranslational peptide folding, elongation regulation, and antibiotics binding. J Mol Biol. 2009;387:502-17 pubmed publisher..In order to explain antibiotics selectivity, action, and resistance, according to these results, differences in the degrees of freedom of the binding regions may need to be considered. ..
- Polacek N, Mankin A. The ribosomal peptidyl transferase center: structure, function, evolution, inhibition. Crit Rev Biochem Mol Biol. 2005;40:285-311 pubmed..Thus, it came as a surprise that recent findings revealed an unexpected high level of variation in the mode of antibiotic binding to the PTC of ribosomes from different organisms. ..
- Lecoq L, Bougault C, Hugonnet J, Veckerlé C, Pessey O, Arthur M, et al. Dynamics induced by ?-lactam antibiotics in the active site of Bacillus subtilis L,D-transpeptidase. Structure. 2012;20:850-61 pubmed publisher..The chemical step of the reaction determines enzyme specificity since no differences in drug affinity were observed. ..
- Meskauskas A, Dinman J. Ribosomal protein L3 functions as a 'rocker switch' to aid in coordinating of large subunit-associated functions in eukaryotes and Archaea. Nucleic Acids Res. 2008;36:6175-86 pubmed publisher..A model is presented describing how all three domains of L3 may function together as a 'rocker switch' to coordinate the stepwise processes of translation elongation. ..
- Simonovic M, Steitz T. A structural view on the mechanism of the ribosome-catalyzed peptide bond formation. Biochim Biophys Acta. 2009;1789:612-23 pubmed publisher..A current understanding of the mechanism of the ribosome-catalyzed peptide bond formation is the focus of this review. Implications on the mechanism of peptide release are discussed as well. ..
- Bentley M, Gaweska H, Kielec J, McCafferty D. Engineering the substrate specificity of Staphylococcus aureus Sortase A. The beta6/beta7 loop from SrtB confers NPQTN recognition to SrtA. J Biol Chem. 2007;282:6571-81 pubmed..These results indicate that the beta6/beta7 loop is an important site for substrate recognition in sortases. ..
- Dunkle J, Xiong L, Mankin A, Cate J. Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action. Proc Natl Acad Sci U S A. 2010;107:17152-7 pubmed publisher..The present data further argue that the identity of nucleotides 752, 2609, and 2055 of 23S ribosomal RNA explain in part the spectrum and selectivity of antibiotic action. ..
- Bhushan S, Meyer H, Starosta A, Becker T, Mielke T, Berninghausen O, et al. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. Mol Cell. 2010;40:138-46 pubmed publisher..Our findings provide direct structural insight into two distinct eukaryotic stalling processes. ..
- Wilson D, Blaha G, Connell S, Ivanov P, Jenke H, Stelzl U, et al. Protein synthesis at atomic resolution: mechanistics of translation in the light of highly resolved structures for the ribosome. Curr Protein Pept Sci. 2002;3:1-53 pubmed..Here we try a systematic synopsis of these ribosomal functions in light of the cryo-electron microscopic structures (resolution >7 A) and the atomic x-ray structures (>2.4 A) of the ribosome. ..
- Meskauskas A, Harger J, Jacobs K, Dinman J. Decreased peptidyltransferase activity correlates with increased programmed -1 ribosomal frameshifting and viral maintenance defects in the yeast Saccharomyces cerevisiae. RNA. 2003;9:982-92 pubmed
- Dubée V, Triboulet S, Mainardi J, Etheve Quelquejeu M, Gutmann L, Marie A, et al. Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt? by carbapenems and cephalosporins. Antimicrob Agents Chemother. 2012;56:4189-95 pubmed publisher..Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition in M. tuberculosis...
- Erlacher M, Lang K, Shankaran N, Wotzel B, Huttenhofer A, Micura R, et al. Chemical engineering of the peptidyl transferase center reveals an important role of the 2'-hydroxyl group of A2451. Nucleic Acids Res. 2005;33:1618-27 pubmed..This implicates a functional or structural role of the 2'-hydroxyl group at A2451 for transpeptidation. ..
- Baram D, Yonath A. From peptide-bond formation to cotranslational folding: dynamic, regulatory and evolutionary aspects. FEBS Lett. 2005;579:948-54 pubmed..Remarkably, although antibiotics discrimination is determined by the identity of a single nucleotide, involved also in resistance, additional nucleotides dictate antibiotics effectiveness. ..
- Wohlgemuth I, Beringer M, Rodnina M. Rapid peptide bond formation on isolated 50S ribosomal subunits. EMBO Rep. 2006;7:699-703 pubmed
- Rohrer S, Berger Bachi B. FemABX peptidyl transferases: a link between branched-chain cell wall peptide formation and beta-lactam resistance in gram-positive cocci. Antimicrob Agents Chemother. 2003;47:837-46 pubmed
- King T, Liu B, McCully R, Fournier M. Ribosome structure and activity are altered in cells lacking snoRNPs that form pseudouridines in the peptidyl transferase center. Mol Cell. 2003;11:425-35 pubmed..The possibility that modifying snoRNPs might affect ribosome structure in other ways is also discussed. ..
- Bøsling J, Poulsen S, Vester B, Long K. Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3. Antimicrob Agents Chemother. 2003;47:2892-6 pubmed..This is the first report of a mechanism of resistance to tiamulin unveiled in molecular detail. ..
- Morlot C, Zapun A, Dideberg O, Vernet T. Growth and division of Streptococcus pneumoniae: localization of the high molecular weight penicillin-binding proteins during the cell cycle. Mol Microbiol. 2003;50:845-55 pubmed..pneumoniae. ..
- Bayfield M, Thompson J, Dahlberg A. The A2453-C2499 wobble base pair in Escherichia coli 23S ribosomal RNA is responsible for pH sensitivity of the peptidyltransferase active site conformation. Nucleic Acids Res. 2004;32:5512-8 pubmed..coli peptidyltransferase center, its lack of conservation makes it, and consequently its near-neutral pK(a), unlikely to contribute to function during peptide bond formation. ..
- Rakauskaite R, Dinman J. rRNA mutants in the yeast peptidyltransferase center reveal allosteric information networks and mechanisms of drug resistance. Nucleic Acids Res. 2008;36:1497-507 pubmed publisher..These studies also add to our understanding of how information is transmitted both locally and over long distances through allosteric networks of rRNA-rRNA and rRNA-protein interactions. ..
- Schmeing T, Huang K, Kitchen D, Strobel S, Steitz T. Structural insights into the roles of water and the 2' hydroxyl of the P site tRNA in the peptidyl transferase reaction. Mol Cell. 2005;20:437-48 pubmed
- Beringer M, Rodnina M. The ribosomal peptidyl transferase. Mol Cell. 2007;26:311-21 pubmed..Proton transfer during the reaction appears to be promoted by a concerted proton shuttle mechanism that involves ribose hydroxyl groups on the tRNA substrate. ..
- Sergiev P, Lesnyak D, Burakovsky D, Kiparisov S, Leonov A, Bogdanov A, et al. Alteration in location of a conserved GTPase-associated center of the ribosome induced by mutagenesis influences the structure of peptidyltransferase center and activity of elongation factor G. J Biol Chem. 2005;280:31882-9 pubmed
- Dorner S, Panuschka C, Schmid W, Barta A. Mononucleotide derivatives as ribosomal P-site substrates reveal an important contribution of the 2'-OH to activity. Nucleic Acids Res. 2003;31:6536-42 pubmed..A model is discussed how further interactions of the 2'-OH in the transition state might influence peptidyl transferase activity. ..
- Erlacher M, Lang K, Wotzel B, Rieder R, Micura R, Polacek N. Efficient ribosomal peptidyl transfer critically relies on the presence of the ribose 2'-OH at A2451 of 23S rRNA. J Am Chem Soc. 2006;128:4453-9 pubmed..These data highlight the unique functional role of the A2451 2'-OH for peptide bond synthesis among all other functional groups at the ribosomal peptidyl transferase active site. ..
- Bieling P, Beringer M, Adio S, Rodnina M. Peptide bond formation does not involve acid-base catalysis by ribosomal residues. Nat Struct Mol Biol. 2006;13:423-8 pubmed..The rate of peptide bond formation with unmodified Phe-tRNA(Phe) is estimated to be >300 s(-1). ..
- Polacek N, Gomez M, Ito K, Xiong L, Nakamura Y, Mankin A. The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. Mol Cell. 2003;11:103-12 pubmed..This indicates that the mechanism of peptide release is distinct from that of peptide bond formation, with A2602 playing a critical role in peptide release during translation termination. ..
- Rakauskaite R, Dinman J. An arc of unpaired "hinge bases" facilitates information exchange among functional centers of the ribosome. Mol Cell Biol. 2006;26:8992-9002 pubmed..We propose that a series of regularly spaced "hinge bases" provide fulcrums around which rigid helices can reorient themselves depending on the occupancy status of the A-site. ..
- Schoonmaker M, Bishai W, Lamichhane G. Nonclassical transpeptidases of Mycobacterium tuberculosis alter cell size, morphology, the cytosolic matrix, protein localization, virulence, and resistance to ?-lactams. J Bacteriol. 2014;196:1394-402 pubmed publisher..tuberculosis to amoxicillin-clavulanate and vancomycin. ..
- Meskauskas A, Dinman J. A molecular clamp ensures allosteric coordination of peptidyltransfer and ligand binding to the ribosomal A-site. Nucleic Acids Res. 2010;38:7800-13 pubmed publisher..The observation that these mutations affected translational fidelity, virus propagation and cell growth demonstrates how small structural changes at the atomic scale can propagate outward to broadly impact the biology of cell. ..
- Amort M, Wotzel B, Bakowska Zywicka K, Erlacher M, Micura R, Polacek N. An intact ribose moiety at A2602 of 23S rRNA is key to trigger peptidyl-tRNA hydrolysis during translation termination. Nucleic Acids Res. 2007;35:5130-40 pubmed..These findings underscore the exceptional functional importance of the ribose moiety at A2602 for triggering peptide release. ..
- Klein D, Moore P, Steitz T. The contribution of metal ions to the structural stability of the large ribosomal subunit. RNA. 2004;10:1366-79 pubmed
- Southworth D, Brunelle J, Green R. EFG-independent translocation of the mRNA:tRNA complex is promoted by modification of the ribosome with thiol-specific reagents. J Mol Biol. 2002;324:611-23 pubmed..These data suggest that molecular targets (ribosomal proteins) in the interface region of the ribosome are critical barriers that influence the translocation of the mRNA:tRNA complex. ..
- Dorner S, Polacek N, Schulmeister U, Panuschka C, Barta A. Molecular aspects of the ribosomal peptidyl transferase. Biochem Soc Trans. 2002;30:1131-6 pubmed..Using modified P-site substrates, we showed that the 2'-OH group of the terminal adenosine is important for peptidyl transfer. These substrates were also used to investigate the metal ion dependency of the peptidyl transferase reaction. ..
- Feinberg J, Joseph S. A conserved base-pair between tRNA and 23 S rRNA in the peptidyl transferase center is important for peptide release. J Mol Biol. 2006;364:1010-20 pubmed
- Peltier J, Courtin P, El Meouche I, Lemee L, Chapot Chartier M, Pons J. Clostridium difficile has an original peptidoglycan structure with a high level of N-acetylglucosamine deacetylation and mainly 3-3 cross-links. J Biol Chem. 2011;286:29053-62 pubmed publisher..The contribution of 3-3 cross-links to peptidoglycan synthesis increased in the presence of ampicillin, indicating that this drug does not inhibit the L,D-transpeptidation pathway in C. difficile. ..
- Selmer M, Dunham C, Murphy F, Weixlbaumer A, Petry S, Kelley A, et al. Structure of the 70S ribosome complexed with mRNA and tRNA. Science. 2006;313:1935-42 pubmed..The interactions of E-site tRNA with the 50S subunit have both similarities and differences compared to those in the archaeal ribosome. The structure also rationalizes much biochemical and genetic data on translation. ..
- Sharma D, Southworth D, Green R. EF-G-independent reactivity of a pre-translocation-state ribosome complex with the aminoacyl tRNA substrate puromycin supports an intermediate (hybrid) state of tRNA binding. RNA. 2004;10:102-13 pubmed..These data establish that pre-translocation-state ribosomes must sample or reside in an intermediate state of tRNA binding independent of the action of EF-G. ..
- Correale S, Ruggiero A, Capparelli R, Pedone E, Berisio R. Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2013;69:1697-706 pubmed publisher..By providing the key interactions in the binding of carbapenem to LdtMt1, this work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antitubercular agents against drug-resistant M. tuberculosis. ..