Genomes and Genes
Summary: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.
- Christophorou M, Castelo Branco G, Halley Stott R, Oliveira C, Loos R, Radzisheuskaya A, et al. Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature. 2014;507:104-8 pubmed publisher..Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction. ..
- Méchin M, Coudane F, Adoue V, Arnaud J, Duplan H, Charveron M, et al. Deimination is regulated at multiple levels including auto-deimination of peptidylarginine deiminases. Cell Mol Life Sci. 2010;67:1491-503 pubmed publisher..In summary, deimination can be regulated at multiple levels: transcription of the PADI genes, translation of the corresponding mRNAs, and auto-deimination of PADs. ..
- Rozaklis T, Beard H, Hassiotis S, Garcia A, Tonini M, Luck A, et al. Impact of high-dose, chemically modified sulfamidase on pathology in a murine model of MPS IIIA. Exp Neurol. 2011;230:123-30 pubmed publisher..If this observation is generally applicable, chemical modification may permit the use of significantly lower doses of lysosomal enzymes in patients currently receiving intravenous enzyme replacement therapy. ..
- Auger I, Martin M, Balandraud N, Roudier J. Rheumatoid arthritis-specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen. Arthritis Rheum. 2010;62:126-31 pubmed publisher..Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4. Most anti-PAD-4-positive sera recognize peptides located both in the N-terminal domain (211-290) and the C-terminal domain (601-650) of PAD-4. ..
- Giuseppe M, Luigia M, Elena P, Yan F, Luigi M. Enzyme promiscuity in the hormone-sensitive lipase family of proteins. Protein Pept Lett. 2012;19:144-54 pubmed..Herein, at first we will describe some general aspects of enzyme promiscuity and then we will report some examples from the ?/? hydrolase superfamily of proteins, with particular emphasis to the hormone-sensitive lipase family. ..
- Liu Y, Chiang Y, Liu G, Hung H. Functional role of dimerization of human peptidylarginine deiminase 4 (PAD4). PLoS ONE. 2011;6:e21314 pubmed publisher..The ionic interaction between Arg8 and Asp547 and the Tyr435-mediated hydrophobic interaction are determinants of PAD4 dimer formation. ..
- Wang L, Chang X, Yuan G, Zhao Y, Wang P. Expression of peptidylarginine deiminase type 4 in ovarian tumors. Int J Biol Sci. 2010;6:454-64 pubmed..The results suggest an important role for PADI4 in the tumorigenesis of ovary cancers that are under the regulation of estrogen. ..
- Leščić Ašler I, Ivic N, Kovačić F, Schell S, Knorr J, Krauss U, et al. Probing enzyme promiscuity of SGNH hydrolases. Chembiochem. 2010;11:2158-67 pubmed publisherSeveral hydrolases of the SGNH superfamily, including the lipase SrLip from Streptomyces rimosus (Q93MW7), the acyl-CoA thioesterase I TesA from Pseudomonas aeruginosa (Q9HZY8) and the two lipolytic enzymes EstA (from P...
- Slack J, Causey C, Thompson P. Protein arginine deiminase 4: a target for an epigenetic cancer therapy. Cell Mol Life Sci. 2011;68:709-20 pubmed publisher..Taken together, these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease. ..
- Cherrington B, Morency E, Struble A, Coonrod S, Wakshlag J. Potential role for peptidylarginine deiminase 2 (PAD2) in citrullination of canine mammary epithelial cell histones. PLoS ONE. 2010;5:e11768 pubmed publisher..This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus...
- Savaraj N, You M, Wu C, Wangpaichitr M, Kuo M, Feun L. Arginine deprivation, autophagy, apoptosis (AAA) for the treatment of melanoma. Curr Mol Med. 2010;10:405-12 pubmed
- Wegner N, Wait R, Sroka A, Eick S, Nguyen K, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and ?-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010;62:2662-72 pubmed publisher..Our results suggest a novel model where P gingivalis-mediated citrullination of bacterial and host proteins provides a molecular mechanism for generating antigens that drive the autoimmune response in RA. ..
- Yu S, Jensen V, Seeliger J, Feldmann I, Weber S, Schleicher E, et al. Structure elucidation and preliminary assessment of hydrolase activity of PqsE, the Pseudomonas quinolone signal (PQS) response protein. Biochemistry. 2009;48:10298-307 pubmed publisher..A crystal complex of the E182A mutant with bis-pNPP was obtained and suggests a catalytic mechanism for hydrolysis. ..
- Auger I, Charpin C, Balandraud N, Martin M, Roudier J. Autoantibodies to PAD4 and BRAF in rheumatoid arthritis. Autoimmun Rev. 2012;11:801-3 pubmed publisher..We observed that anti PAD4 are inhibitory whereas anti BRAF stimulate BRAF activity. Anti PAD4 and anti BRAF antibodies may be used to diagnose RA, particularly in the absence of anti citrullinated protein antibodies. ..
- Chen J, Cheng C, Xia Y, Zhao H, Fang C, Shan Y, et al. Lmo0036, an ornithine and putrescine carbamoyltransferase in Listeria monocytogenes, participates in arginine deiminase and agmatine deiminase pathways and mediates acid tolerance. Microbiology. 2011;157:3150-61 pubmed publisher..5), and corresponded to a loss in ammonia production, indicating that Lmo0036 was responsible for acid tolerance at both sublethal and lethal pH levels. Furthermore, Lmo0036 played a possible role in Listeria virulence...
- Knapik A, Petkowski J, Otwinowski Z, Cymborowski M, Cooper D, Majorek K, et al. A multi-faceted analysis of RutD reveals a novel family of ?/? hydrolases. Proteins. 2012;80:2359-68 pubmed publisher..This approach also revealed that RutD represents a previously undescribed family within the ?/? hydrolases. We compare and contrast RutD with PcaD, which is the closest structural homolog to RutD...
- Chaloupkova R, Prokop Z, Sato Y, Nagata Y, Damborsky J. Stereoselectivity and conformational stability of haloalkane dehalogenase DbjA from Bradyrhizobium japonicum USDA110: the effect of pH and temperature. FEBS J. 2011;278:2728-38 pubmed publisher..Unique catalytic activity and structural stability of DbjA in a broad pH range, combined with high enantioselectivity with particular substrates, make this enzyme a very versatile biocatalyst. Enzyme EC126.96.36.199 haloalkane dehalogenase...
- Jang B, Shin H, Choi J, Nguyen D, Jeong B, Ishigami A, et al. Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins. J Neuropathol Exp Neurol. 2011;70:116-24 pubmed publisher..Our findings suggest that different subcellular compartmentalization of PAD2 and citrullinated proteins may have different physiological roles in normal and neurodegenerative conditions. ..
- Knuckley B, Causey C, Jones J, Bhatia M, Dreyton C, Osborne T, et al. Substrate specificity and kinetic studies of PADs 1, 3, and 4 identify potent and selective inhibitors of protein arginine deiminase 3. Biochemistry. 2010;49:4852-63 pubmed publisher..Additionally, the substrate specificity studies provided critical information that aided the identification of PAD3-selective inhibitors. These compounds, denoted F4- and Cl4-amidine, are the most potent PAD3 inhibitors ever described. ..
- Koudelakova T, Chovancova E, Brezovsky J, Monincová M, Fortova A, Jarkovsky J, et al. Substrate specificity of haloalkane dehalogenases. Biochem J. 2011;435:345-54 pubmed publisher..The identification of other structural determinants of the substrate specificity remains a challenge for further research on haloalkane dehalogenases...
- Simon G, Cravatt B. Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study. J Biol Chem. 2010;285:11051-5 pubmed publisher..protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.
- Heron B, Mikaeloff Y, Froissart R, Caridade G, Maire I, Caillaud C, et al. Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A. 2011;155A:58-68 pubmed publisher..Notwithstanding the rapidity of further clinical deterioration, all MPSIII patients suffer early onset devastating neurological manifestations that deserve early treatment when available. ..
- DeNoel P, Philipp M, Doyle L, Martin D, Carletti G, Poolman J. A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae. Vaccine. 2011;29:5495-501 pubmed publisher..In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies. ..
- Darrah E, Rosen A, Giles J, Andrade F. Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: novel insights into autoantigen selection in rheumatoid arthritis. Ann Rheum Dis. 2012;71:92-8 pubmed publisher..The studies provide evidence that PAD enzymes have the intrinsic capacity to select unique protein targets. The authors propose that unique PAD specificity may play a role in autoantigen selection in RA. ..
- Drienovska I, Chovancova E, Koudelakova T, Damborsky J, Chaloupkova R. Biochemical characterization of a novel haloalkane dehalogenase from a cold-adapted bacterium. Appl Environ Microbiol. 2012;78:4995-8 pubmed publisher..DpcA exhibited a unique temperature profile with exceptionally high activities at low temperatures. The psychrophilic properties of DpcA make this enzyme promising for various environmental applications...
- Shimada N, Handa S, Uchida Y, Fukuda M, Maruyama N, Asaga H, et al. Developmental and age-related changes of peptidylarginine deiminase 2 in the mouse brain. J Neurosci Res. 2010;88:798-806 pubmed publisher..These findings indicate that, despite PAD2's normally inactive status, it becomes active and citrullinates cellular proteins, but only when the intracellular Ca(2+) balance is upset during neurodegenerative changes. ..
- Zhang X, Bolt M, Guertin M, Chen W, Zhang S, Cherrington B, et al. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor ? target gene activation. Proc Natl Acad Sci U S A. 2012;109:13331-6 pubmed publisher..Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ER?, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation. ..
- Landete J, Arena M, Pardo I, Manca de Nadra M, Ferrer S. The role of two families of bacterial enzymes in putrescine synthesis from agmatine via agmatine deiminase. Int Microbiol. 2010;13:169-77 pubmed..This paper also discusses the role of the agmatine deiminase system (AgDS) in acid stress resistance. ..
- Kan R, Yurttas P, Kim B, Jin M, Wo L, Lee B, et al. Regulation of mouse oocyte microtubule and organelle dynamics by PADI6 and the cytoplasmic lattices. Dev Biol. 2011;350:311-22 pubmed publisher..These results demonstrate that the PADI6/CPL superstructure plays a key role in regulating MT-mediated organelle positioning and movement. ..
- Auldridge M, Guo Y, Austin M, Ramsey J, Fridman E, Pichersky E, et al. Emergent decarboxylase activity and attenuation of ?/?-hydrolase activity during the evolution of methylketone biosynthesis in tomato. Plant Cell. 2012;24:1596-607 pubmed publisher..Furthermore, we employ structure-guided mutagenesis and functional assays to demonstrate that MKS1, unlike enzymes from this hydrolase superfamily, is not an efficient hydrolase but instead catalyzes the decarboxylation of 3-keto acids...
- Zhang X, Gamble M, Stadler S, Cherrington B, Causey C, Thompson P, et al. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells. PLoS Genet. 2011;7:e1002112 pubmed publisher..These results define a novel role for PADI4 as a transcription factor co-activator. ..
- Kelly M, Jungbluth A, Wu B, Bomalaski J, Old L, Ritter G. Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase. Br J Cancer. 2012;106:324-32 pubmed publisher..These results suggest a role for ADI-PEG20 in the treatment of SCLC, and a clinical trial exploring this therapeutic approach in patients with ASS-negative SCLC by IHC has now been initiated. ..
- Pogorelko G, Fursova O, Lin M, Pyle E, Jass J, Zabotina O. Post-synthetic modification of plant cell walls by expression of microbial hydrolases in the apoplast. Plant Mol Biol. 2011;77:433-45 pubmed publisher..creation of defined cell wall modifications in the model plant Arabidopsis thaliana by expression of microbial hydrolases with known specific activities is a promising approach to examine the impacts of cell wall composition and ..
- Fan L, He D, Wang Q, Zong M, Zhang H, Yang L, et al. Citrullinated vimentin stimulates proliferation, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression of fibroblast-like synoviocytes in rheumatoid arthritis. Scand J Rheumatol. 2012;41:354-8 pubmed publisher..cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients. ..
- Waters M, Scaffidi A, Flematti G, Smith S. Karrikins force a rethink of strigolactone mode of action. Plant Signal Behav. 2012;7:969-72 pubmed publisher..Here we rationalise these observations into a hypothesis whereby different ?/?-hydrolases distinguish SL and KAR by virtue of their non-butenolide moieties and catalyze nucleophilic attack on the ..
- Li P, Hu J, Wang Y. Methods for analyzing histone citrullination in chromatin structure and gene regulation. Methods Mol Biol. 2012;809:473-88 pubmed publisher..These methods would be useful techniques to study this unique histone modification. ..
- Mangat P, Wegner N, Venables P, Potempa J. Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?. Arthritis Res Ther. 2010;12:209 pubmed publisher..Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis. ..
- Li P, Li M, Lindberg M, Kennett M, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207:1853-62 pubmed publisher..Our results define a role for histone hypercitrullination in innate immunity during bacterial infection. ..
- You M, Savaraj N, Wangpaichitr M, Wu C, Kuo M, Varona Santos J, et al. The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines. Biochem Biophys Res Commun. 2010;394:760-6 pubmed publisher..We propose that these two drugs can complement each other by activating the intrinsic and extrinsic apoptosis pathways, thus enhance the killing of melanoma cells. ..
- Carrillo Vico A, Leech M, Anderton S. Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system. J Immunol. 2010;184:2839-46 pubmed publisher..The PAD2 and PAD4 enzymes were markedly upregulated in the inflamed CNS. Therefore, once inflammation is established, citrullination of target autoantigens can allow an expanded repertoire of T cells to contribute to CNS pathology. ..
- Causey C, Jones J, Slack J, Kamei D, Jones L, Subramanian V, et al. The development of N-?-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-?-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) in. J Med Chem. 2011;54:6919-35 pubmed publisher..Relative to F- and Cl-amidine, the compounds also show enhanced potency in cellulo. As such, these compounds will be versatile chemical probes of PAD function. ..
- Knuckley B, Jones J, Bachovchin D, Slack J, Causey C, Brown S, et al. A fluopol-ABPP HTS assay to identify PAD inhibitors. Chem Commun (Camb). 2010;46:7175-7 pubmed publisher..Using this assay, streptonigrin was identified as a potent, selective, and irreversible PAD4 inactivator. ..
- Gupta R, Goldsmith M, Ashani Y, Simo Y, Mullokandov G, Bar H, et al. Directed evolution of hydrolases for prevention of G-type nerve agent intoxication. Nat Chem Biol. 2011;7:120-5 pubmed publisher..We then demonstrated the in vivo prophylactic activity of an evolved variant. These evolved variants and the newly developed screens provide the basis for engineering PON1 for prophylaxis against other G-type agents. ..
- Jang B, Jeon Y, Choi J, Park M, Kim J, Ishigami A, et al. Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination: links between altered multifunction of enolase and neurodegenerative diseases. Biochem J. 2012;445:183-92 pubmed publisher..These findings suggest that PAD-mediated citrullination regulates the diverse physiological activities of enolase and that CE may be a candidate diagnostic/prognostic factor for degenerative diseases. ..
- Pollmann S, Stensland M, Halvorsen E, Sollid L, Kvien T, Fleckenstein B, et al. Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate. Rheumatol Int. 2012;32:1271-6 pubmed publisher..However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA. ..
- PAULK N, Wursthorn K, Wang Z, Finegold M, Kay M, Grompe M. Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo. Hepatology. 2010;51:1200-8 pubmed publisher..In this model, repaired hepatocytes have a selective growth advantage and are thus able to proliferate to efficiently repopulate mutant livers and cure the underlying metabolic disease...