Summary: A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.

Top Publications

  1. Mohanty D, Sankaranarayanan R, Gokhale R. Fatty acyl-AMP ligases and polyketide synthases are unique enzymes of lipid biosynthetic machinery in Mycobacterium tuberculosis. Tuberculosis (Edinb). 2011;91:448-55 pubmed publisher lipid biosynthesis that have established functional role of polyketide synthases (PKSs) and fatty acyl-AMP ligases (FAALs)...
  2. Bagby S, Bergman N, Shechner D, Yen C, Bartel D. A class I ligase ribozyme with reduced Mg2+ dependence: Selection, sequence analysis, and identification of functional tertiary interactions. RNA. 2009;15:2129-46 pubmed publisher
  3. Miura K, Lee J, Gong Q, Ma S, Jin J, Yoo C, et al. SIZ1 regulation of phosphate starvation-induced root architecture remodeling involves the control of auxin accumulation. Plant Physiol. 2011;155:1000-12 pubmed publisher
    ..Together, these results suggest that SIZ1 negatively regulates Pi starvation-induced root architecture remodeling through the control of auxin patterning. ..
  4. Carrano A, Liu Z, Dillin A, Hunter T. A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature. 2009;460:396-9 pubmed publisher
    ..Taken together, our results indicate that WWP-1 and UBC-18 function to ubiquitinate substrates that regulate diet-restriction-induced longevity. ..
  5. Krol E, Becker A. ppGpp in Sinorhizobium meliloti: biosynthesis in response to sudden nutritional downshifts and modulation of the transcriptome. Mol Microbiol. 2011;81:1233-54 pubmed publisher
    ..dksA was required for the majority of the relA-dependent regulations...
  6. Ling Y, Zhang C, Chen T, Hao H, Liu P, Bressan R, et al. Mutation in SUMO E3 ligase, SIZ1, disrupts the mature female gametophyte in Arabidopsis. PLoS ONE. 2012;7:e29470 pubmed publisher
    ..Together, our results suggest that SIZ1 sustains the stability and normal function of the mature female gametophyte which is necessary for pollen tube guidance. ..
  7. Slavoff S, Liu D, Cohen J, Ting A. Imaging protein-protein interactions inside living cells via interaction-dependent fluorophore ligation. J Am Chem Soc. 2011;133:19769-76 pubmed publisher
    ..ID-PRIME provides a powerful and complementary approach to existing methods for visualization of PPIs in living cells with spatial and temporal resolution. ..
  8. Das B, Pal R, Bag S, Bhadra R. Stringent response in Vibrio cholerae: genetic analysis of spoT gene function and identification of a novel (p)ppGpp synthetase gene. Mol Microbiol. 2009;72:380-98 pubmed publisher
    ..Analysis of a V. choleraeDeltarelADeltaspoTDeltarelV triple mutant confirmed that apart from canonical relA and spoT genes, relV is a novel gene in V. cholerae responsible for (p)ppGpp synthesis...
  9. Oza S, Chen S, Wyllie S, Coward J, Fairlamb A. ATP-dependent ligases in trypanothione biosynthesis--kinetics of catalysis and inhibition by phosphinic acid pseudopeptides. FEBS J. 2008;275:5408-21 pubmed publisher
    ..This phosphinate analogue remains the most potent enzyme inhibitor identified to date, and represents a good starting point for drug discovery for trypanosomiasis and leishmaniasis. ..

More Information


  1. Chen Q, Zhang B, Hicks L, Wang S, Jez J. A liquid chromatography-tandem mass spectrometry-based assay for indole-3-acetic acid-amido synthetase. Anal Biochem. 2009;390:149-54 pubmed publisher
    ..Compared with previously described LC- and thin-layer chromatography (TLC)-based assays, this LC-MS/MS method provides a robust and sensitive means for performing direct kinetic studies on a range of IAA-conjugating enzymes. ..
  2. Steindler L, Bertani I, De Sordi L, Schwager S, Eberl L, Venturi V. LasI/R and RhlI/R quorum sensing in a strain of Pseudomonas aeruginosa beneficial to plants. Appl Environ Microbiol. 2009;75:5131-40 pubmed publisher
    ..This is an in-depth genetic and molecular study of QS in an environmental P. aeruginosa strain and highlights several differences with QS regulation in the clinical isolate PAO1. ..
  3. Ghosh S, Sureka K, Ghosh B, Bose I, Basu J, Kundu M. Phenotypic heterogeneity in mycobacterial stringent response. BMC Syst Biol. 2011;5:18 pubmed publisher
    ..The results of the theoretical model along with a comprehensive analysis of the flow cytometry data provide definitive evidence for the coexistence of two subpopulations with overlapping protein distributions. ..
  4. Park B, Song J, Seo H. Arabidopsis nitrate reductase activity is stimulated by the E3 SUMO ligase AtSIZ1. Nat Commun. 2011;2:400 pubmed publisher
    ..Both sumoylated and non-sumoylated NIA1 and NIA2 can form dimers. Our results indicate that AtSIZ1 positively controls nitrogen assimilation by promoting sumoylation of NRs in Arabidopsis. ..
  5. Yao J, Uttamapinant C, Poloukhtine A, Baskin J, Codelli J, Sletten E, et al. Fluorophore targeting to cellular proteins via enzyme-mediated azide ligation and strain-promoted cycloaddition. J Am Chem Soc. 2012;134:3720-8 pubmed publisher
  6. O Grady E, Viteri D, Malott R, Sokol P. Reciprocal regulation by the CepIR and CciIR quorum sensing systems in Burkholderia cenocepacia. BMC Genomics. 2009;10:441 pubmed publisher
    ..cenocepacia have been identified. The two quorum sensing systems exert reciprocal regulation of many genes likely enabling fine-tuned control of quorum sensing gene expression in B. cenocepacia strains carrying the cenocepacia island. ..
  7. Shachrai I, Zaslaver A, Alon U, Dekel E. Cost of unneeded proteins in E. coli is reduced after several generations in exponential growth. Mol Cell. 2010;38:758-67 pubmed publisher
  8. Miura K, Lee J, Miura T, Hasegawa P. SIZ1 controls cell growth and plant development in Arabidopsis through salicylic acid. Plant Cell Physiol. 2010;51:103-13 pubmed publisher
    ..These results indicate that SIZ1 regulates cell growth and plant development with regulation of SA accumulation. Also, XTH8 and XTH31 genes may be responsible for reduced leaf cell expansion. ..
  9. Uttamapinant C, White K, Baruah H, Thompson S, Fernandez Suarez M, Puthenveetil S, et al. A fluorophore ligase for site-specific protein labeling inside living cells. Proc Natl Acad Sci U S A. 2010;107:10914-9 pubmed publisher
    ..By genetically targeting the PRIME ligase to specific subcellular compartments, we were able to selectively label spatially distinct subsets of proteins, such as the surface pool of neurexin and the nuclear pool of actin. ..
  10. Battesti A, Bouveret E. Bacteria possessing two RelA/SpoT-like proteins have evolved a specific stringent response involving the acyl carrier protein-SpoT interaction. J Bacteriol. 2009;191:616-24 pubmed publisher
    ..This suggests that bacteria have evolved several different modes of (p)ppGpp regulation in order to respond to nutrient starvation. ..
  11. Teixeira L, Reed S. Ubiquitin ligases and cell cycle control. Annu Rev Biochem. 2013;82:387-414 pubmed publisher
    ..These functions are primarily carried out by two families of E3 ubiquitin ligases, the Skp/cullin/F-box-containing and anaphase-promoting complex/cyclosome complexes...
  12. Cheong M, Park H, Hong M, Lee J, Choi W, Jin J, et al. Specific domain structures control abscisic acid-, salicylic acid-, and stress-mediated SIZ1 phenotypes. Plant Physiol. 2009;151:1930-42 pubmed publisher
    ..PIAS (for protein inhibitor of activated STAT) and yeast SIZ SUMO (for small ubiquitin-related modifier) E3 ligases in Arabidopsis (Arabidopsis thaliana)...
  13. Geiger T, Goerke C, Fritz M, Schäfer T, Ohlsen K, Liebeke M, et al. Role of the (p)ppGpp synthase RSH, a RelA/SpoT homolog, in stringent response and virulence of Staphylococcus aureus. Infect Immun. 2010;78:1873-83 pubmed publisher
    ..These results indicate that stringent conditions are present during infection and that RSH-dependent derepression of CodY-regulated genes is essential for virulence in S. aureus. ..
  14. Babic F, Venturi V, Maravic Vlahovicek G. Tobramycin at subinhibitory concentration inhibits the RhlI/R quorum sensing system in a Pseudomonas aeruginosa environmental isolate. BMC Infect Dis. 2010;10:148 pubmed publisher
    ..aeruginosa will highlight possible inter-species signalling taking place in nature and can possible also have important implications in the mode of utilization for human use of this very important antibiotic. ..
  15. Miura K, Ohta M. SIZ1, a small ubiquitin-related modifier ligase, controls cold signaling through regulation of salicylic acid accumulation. J Plant Physiol. 2010;167:555-60 pubmed publisher
    ..As well as siz1, another SA-accumulating mutant acd6 exhibited freezing sensitivity and the sensitivity was suppressed in acd6 nahG plants. Taken together, these data indicate that SA is involved in regulation of cold signaling. ..
  16. Patin D, Boniface A, Kova A, Herv M, Dementin S, Barreteau H, et al. Purification and biochemical characterization of Mur ligases from Staphylococcus aureus. Biochimie. 2010;92:1793-800 pubmed publisher
    The Mur ligases (MurC, MurD, MurE and MurF) catalyze the stepwise synthesis of the UDP-N-acetylmuramoyl-pentapeptide precursor of peptidoglycan...
  17. Wolz C, Geiger T, Goerke C. The synthesis and function of the alarmone (p)ppGpp in firmicutes. Int J Med Microbiol. 2010;300:142-7 pubmed publisher
    ..Here we will focus on basic differences between firmicutes and proteobacteria, particularly E. coli. ..
  18. Natori Y, Tagami K, Murakami K, Yoshida S, Tanigawa O, Moh Y, et al. Transcription activity of individual rrn operons in Bacillus subtilis mutants deficient in (p)ppGpp synthetase genes, relA, yjbM, and ywaC. J Bacteriol. 2009;191:4555-61 pubmed publisher
  19. Zhou Y, Coleman W, Yang Z, Yang Y, Hodgson N, Chen F, et al. Regulation of cell growth during serum starvation and bacterial survival in macrophages by the bifunctional enzyme SpoT in Helicobacter pylori. J Bacteriol. 2008;190:8025-32 pubmed publisher
    ..The unique role of (p)ppGpp in cell growth during serum starvation, in the stress response, and in the persistence of H. pylori is discussed. ..
  20. English B, Hauryliuk V, Sanamrad A, Tankov S, Dekker N, Elf J. Single-molecule investigations of the stringent response machinery in living bacterial cells. Proc Natl Acad Sci U S A. 2011;108:E365-73 pubmed publisher
  21. Sun D, Lee G, Lee J, Kim H, Rhee H, Park S, et al. A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses. Nat Struct Mol Biol. 2010;17:1188-94 pubmed publisher
    ..These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses. ..
  22. Gaca A, Abranches J, Kajfasz J, LEMOS J. Global transcriptional analysis of the stringent response in Enterococcus faecalis. Microbiology. 2012;158:1994-2004 pubmed publisher
    ..Thus, while ?relA and ?relA?relQ cannot use (p)ppGpp to sense and respond to stresses, fitness of ?relA?relQ may be further impaired due to an unbalanced metabolism. ..
  23. Liu D, Tangpeerachaikul A, Selvaraj R, Taylor M, Fox J, Ting A. Diels-Alder cycloaddition for fluorophore targeting to specific proteins inside living cells. J Am Chem Soc. 2012;134:792-5 pubmed publisher
    ..By incorporating the Diels-Alder cycloaddition, we have broadened the panel of fluorophores that can be targeted by lipoic acid ligase. ..
  24. Atkinson G, Tenson T, Hauryliuk V. The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life. PLoS ONE. 2011;6:e23479 pubmed publisher
    ..Such signals may be transmitted via NTD to CTD intra-molecular interactions, or inter-molecular interactions either among individual RSH molecules or among long RSHs and other binding partners such as the ribosome. ..
  25. Dengler V, Meier P, Heusser R, Kupferschmied P, Fazekas J, Friebe S, et al. Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response. FEMS Microbiol Lett. 2012;333:109-20 pubmed publisher
    ..Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis. ..
  26. Albuquerque C, Wang G, Lee N, Kolodner R, Putnam C, Zhou H. Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements. PLoS Genet. 2013;9:e1003670 pubmed publisher
    ..Thus, distinct SUMO ligases work in concert with Esc2 and Slx5-Slx8 to control substrate specificity and sumoylation homeostasis to prevent ..
  27. Wexselblatt E, Katzhendler J, Saleem Batcha R, Hansen G, Hilgenfeld R, Glaser G, et al. ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria. Bioorg Med Chem. 2010;18:4485-97 pubmed publisher
    ..As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. ..
  28. Qiao H, Prasada Rao H, Yang Y, Fong J, Cloutier J, Deacon D, et al. Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nat Genet. 2014;46:194-9 pubmed publisher
    ..We suggest that SUMO and ubiquitin have antagonistic roles during meiotic recombination that are balanced to effect differential stabilization of recombination factors at crossover and non-crossover sites. ..
  29. Dawlaty J, Zhang X, Fischbach M, Clardy J. Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases. J Nat Prod. 2010;73:441-6 pubmed publisher
    ..The dapdiamide family's promiscuous biosynthetic pathway contains two unconventional amide ligases that are predicted to couple its constituent monomers.
  30. Puthenveetil S, Liu D, White K, Thompson S, Ting A. Yeast display evolution of a kinetically efficient 13-amino acid substrate for lipoic acid ligase. J Am Chem Soc. 2009;131:16430-8 pubmed publisher
    ..The kinetic improvement over LAP1 allowed us to rapidly label cell surface peptide-fused receptors with quantum dots. ..
  31. Miura K, Lee J, Jin J, Yoo C, Miura T, Hasegawa P. Sumoylation of ABI5 by the Arabidopsis SUMO E3 ligase SIZ1 negatively regulates abscisic acid signaling. Proc Natl Acad Sci U S A. 2009;106:5418-23 pubmed publisher
    ..The double mutant siz1-2 afp-1 exhibited even greater ABA sensitivity than the single mutant siz1, suggesting that SIZ1 represses ABI5 signaling function independent of AFP1. ..
  32. Ishida T, Yoshimura M, Miura K, Sugimoto K. MMS21/HPY2 and SIZ1, two Arabidopsis SUMO E3 ligases, have distinct functions in development. PLoS ONE. 2012;7:e46897 pubmed publisher
    ..To date, multiple families of SUMO E3 ligases have been reported in yeast and animals, but only two types of E3 ligases have been identified in Arabidopsis: ..
  33. Schmidt S, Blom J, Pernthaler J, Berg G, Baldwin A, Mahenthiralingam E, et al. Production of the antifungal compound pyrrolnitrin is quorum sensing-regulated in members of the Burkholderia cepacia complex. Environ Microbiol. 2009;11:1422-37 pubmed publisher
    ..Using fusions of the lacZ gene to the promoter of the prnABCD operon, which directs the synthesis of prn, we demonstrate that expression of prn is positively regulated by CepR at the level of transcription. ..
  34. Pinta E, Li Z, Batzilla J, Pajunen M, Kasanen T, Rabsztyn K, et al. Identification of three oligo-/polysaccharide-specific ligases in Yersinia enterocolitica. Mol Microbiol. 2012;83:125-36 pubmed publisher
    ..The LPS phenotypes of Y. enterocolitica O:3 single, double and triple ligase mutants indicated that two of ligases, named as WaaL(os) and WaaL(ps) , had a preferred substrate specificity for OC and O-PS, respectively, although ..
  35. Abranches J, Martinez A, Kajfasz J, Chavez V, Garsin D, LEMOS J. The molecular alarmone (p)ppGpp mediates stress responses, vancomycin tolerance, and virulence in Enterococcus faecalis. J Bacteriol. 2009;191:2248-56 pubmed publisher
    ..Taken together, these results indicate that (p)ppGpp pools modulate environmental stress responses, vancomycin tolerance, and virulence in this important nosocomial pathogen. ..
  36. Dalebroux Z, Edwards R, Swanson M. SpoT governs Legionella pneumophila differentiation in host macrophages. Mol Microbiol. 2009;71:640-58 pubmed publisher
    ..Thus, L. pneumophila requires SpoT to monitor FAB and to alternate between replication and transmission in macrophages...
  37. Lucanic M, Kapahi P. Ubiquitin ligases join the field of dietary restriction in C.elegans. Aging (Albany NY). 2009;1:751-2 pubmed
  38. Hermes F, Cronan J. Scavenging of cytosolic octanoic acid by mutant LplA lipoate ligases allows growth of Escherichia coli strains lacking the LipB octanoyltransferase of lipoic acid synthesis. J Bacteriol. 2009;191:6796-803 pubmed publisher
    ..The LplA proteins encoded by the mutant genes have reduced K(m) values for free octanoic acid and thus are able to scavenge cytosolic octanoic acid for octanoylation of lipoyl domains. ..
  39. Sajish M, Kalayil S, Verma S, Nandicoori V, Prakash B. The significance of EXDD and RXKD motif conservation in Rel proteins. J Biol Chem. 2009;284:9115-23 pubmed publisher
  40. Baruah H, Puthenveetil S, Choi Y, Shah S, Ting A. An engineered aryl azide ligase for site-specific mapping of protein-protein interactions through photo-cross-linking. Angew Chem Int Ed Engl. 2008;47:7018-21 pubmed publisher
  41. Kume K, Iizumi Y, Shimada M, Ito Y, Kishi T, Yamaguchi Y, et al. Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway. Genes Cells. 2010;15:339-49 pubmed publisher
    ..Here, we show evidence that UBR1 and UBR2 might be cellular targets of leucine. UBR1 and UBR2 are E3 ubiquitin ligases that recognize the identity of N-terminal residues and contribute to selective destabilization of target proteins ..
  42. Chen C, Chen Y, Tang I, Liang H, Lai C, Chiou J, et al. Arabidopsis SUMO E3 ligase SIZ1 is involved in excess copper tolerance. Plant Physiol. 2011;156:2225-34 pubmed publisher
    ..These data suggest that SIZ1-mediated sumoylation is involved specifically in copper homeostasis and tolerance in planta. ..
  43. Gamage A, Shui G, Wenk M, Chua K. N-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilm formation of Burkholderia pseudomallei. Microbiology. 2011;157:1176-86 pubmed publisher
    ..We propose that exogenous OHC8HL antagonizes biofilm formation in B. pseudomallei, possibly by competing with endogenous C8HL for binding to BpsR. ..
  44. Saracco S, Miller M, Kurepa J, Vierstra R. Genetic analysis of SUMOylation in Arabidopsis: conjugation of SUMO1 and SUMO2 to nuclear proteins is essential. Plant Physiol. 2007;145:119-34 pubmed
    ..Taken together, it appears that SIZ1-mediated conjugation of SUMO1 and SUMO2 to other intracellular proteins is essential in Arabidopsis, possibly through stress-induced modification of a potentially diverse pool of nuclear proteins. ..
  45. Lemos J, Lin V, Nascimento M, Abranches J, Burne R. Three gene products govern (p)ppGpp production by Streptococcus mutans. Mol Microbiol. 2007;65:1568-81 pubmed publisher
  46. Kim J, Feng H, Kipreos E. C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway. Curr Biol. 2007;17:966-72 pubmed
    ..This demonstrates that CDC-6 translocation is critical for preventing rereplication and that CUL-4 independently controls both replication-licensing factors. ..
  47. Qiu X, Fay D. ARI-1, an RBR family ubiquitin-ligase, functions with UBC-18 to regulate pharyngeal development in C. elegans. Dev Biol. 2006;291:239-52 pubmed
    ..elegans. In order to identify ubiquitin-ligases acting downstream of UBC-18, we carried out a two-hybrid screen using UBC-18 as the bait molecule...
  48. Levy M, Griswold K, Ellington A. Direct selection of trans-acting ligase ribozymes by in vitro compartmentalization. RNA. 2005;11:1555-62 pubmed
  49. Moris M, Braeken K, Schoeters E, Verreth C, Beullens S, Vanderleyden J, et al. Effective symbiosis between Rhizobium etli and Phaseolus vulgaris requires the alarmone ppGpp. J Bacteriol. 2005;187:5460-9 pubmed
    ..etli relA mutant. Our results suggest that relA may play an important role in the regulation of gene expression in R. etli bacteroids and in the adaptation of bacteroid physiology...
  50. Miura K, Jin J, Lee J, Yoo C, Stirm V, Miura T, et al. SIZ1-mediated sumoylation of ICE1 controls CBF3/DREB1A expression and freezing tolerance in Arabidopsis. Plant Cell. 2007;19:1403-14 pubmed
    ..SIZ1-dependent sumoylation of ICE1 may activate and/or stabilize the protein, facilitating expression of CBF3/DREB1A and repression of MYB15, leading to low temperature tolerance...
  51. Traxler M, Chang D, Conway T. Guanosine 3',5'-bispyrophosphate coordinates global gene expression during glucose-lactose diauxie in Escherichia coli. Proc Natl Acad Sci U S A. 2006;103:2374-9 pubmed
  52. Gould T, Herman J, Krank J, Murphy R, Churchill M. Specificity of acyl-homoserine lactone synthases examined by mass spectrometry. J Bacteriol. 2006;188:773-83 pubmed
    ..Furthermore, these studies offer additional methods that will be useful for surveying and quantitating AHLs from different sources. ..
  53. Tomlin K, Malott R, Ramage G, Storey D, Sokol P, Ceri H. Quorum-sensing mutations affect attachment and stability of Burkholderia cenocepacia biofilms. Appl Environ Microbiol. 2005;71:5208-18 pubmed