The nitrilase superfamily: classification, structure and function
© BioMed Central Ltd 2001
Published: 15 January 2001
The nitrilase superfamily consists of thiol enzymes involved in natural product biosynthesis and post-translational modification in plants, animals, fungi and certain prokaryotes. On the basis of sequence similarity and the presence of additional domains, the superfamily can be classified into 13 branches, nine of which have known or deduced specificity for specific nitrile- or amide-hydrolysis or amide-condensation reactions. Genetic and biochemical analysis of the family members and their associated domains assists in predicting the localization, specificity and cell biology of hundreds of uncharacterized protein sequences.
Plants, animals and fungi perform a wide variety of nonpeptide carbon-nitrogen hydrolysis reactions using members of the nitrilase superfamily of enzymes. These nitrilase [1,2] and amidase [3,4] reactions, which produce auxin, biotin, β-alanine and other natural products, and which result in deamination of protein and amino acid substrates, all involve attack of a cyano or carbonyl carbon by a conserved cysteine [5,6]. Many bacteria and archaea, particularly those with an ecological relationship to plants and animals, encode members of the nitrilase superfamily and utilize the enzymes for chemically similar nitrile or amide hydrolysis reactions or for condensation of acyl chains to polypeptide amino termini.
On the basis of global and structure-based sequence analysis, members of the nitrilase superfamily can now be classified into 13 branches and the substrate specificity of members of nine branches can be anticipated. Despite historical classification of all of these sequences as nitrilase-related, only one branch is known to have nitrilase activity, whereas eight branches have apparent amidase or amide-condensation activities. Members of seven branches of the nitrilase superfamily have participated in domain fusion events that alter the localization of the nitrilase-related domain, link ammonia production to ammonia consumption, or potentially link proteins involved in cellular signaling. For example, fusion of domains we expect to have glutamine amidohydrolase (GAT) activity to some bacterial and all eukaryotic nicotinamide adenine dinucleotide (NAD) synthetases can account for the previously unsolved problem that only some NAD synthetases use glutamine as a source of ammonia [7,8,9]. Remarkably, these fusions contain the fourth apparent GAT domain involved in coupled amide transfer reactions as they are unrelated to other GAT-domain-containing families: the amino-terminal nucleophile (Ntn) hydrolases and triad amidotransferases , and the amidase signature family . Crystal structures of two nitrilase superfamily members - worm NitFhit  and a bacterial N-carbamyl-D-amino acid amidohydrolase  - reveal that nitrilase-related proteins are multimeric α-β-β-α sandwich proteins that have a conserved Glu-Lys-Cys catalytic triad responsible for covalent catalysis. Mutating catalytic triad residues may allow substrates to be trapped and identified for the branches that remain to be characterized biochemically.
Evolution and classification
Members of the nitrilase superfamily appear to be found in all plants, animals and fungi, and many of these organisms have multiple nitrilase-related proteins from more than one branch of the superfamily. Nitrilase-related sequences are also found in phylogenetically isolated prokaryotes that appear to have an ecological relationship to plants and animals. The nitrilase superfamily therefore probably emerged prior to the separation of plants, animals and fungi, radiated into families, and then spread laterally to bacteria and archaea. Some branches of the nitrilase superfamily are found only in prokaryotes; members of these branches may constitute rational antibiotic targets.
Automated sequence searching easily identifies predicted polypeptides as members of the nitrilase superfamily, but many database annotations have been applied haphazardly. Because members of the nitrilase superfamily are reported to be nitrilases, aliphatic amidases, β-ureidopropionases, β-alanine synthases, N-carbamyl-D-amino acid amidohydrolases and so on, these designations appear in the sequence-definition lines of multiple databases, often irrespective of the activity of the most closely related characterized enzyme.
Summary of the enzyme activities of the nitrilase superfamily
1 - Nitrilase
2 - Aliphatic amidase
3 - Amino-terminal amidase
4 - Biotinidase
6 - Carbamylase Yes
7 - Prokaryote NAD synthetase
8 - Eukaryote NAD synthetase
9 - Apolipoprotein N-acyltransferase
10 -Nit and Nitfhit
13 -Nonfused outliers
Domain fusions in the nitrilase superfamily
Two independently derived families of GAT domains have been found in a variety of two-domain polypeptides that couple ammonia hydrolysis from glutamine to ammonia consumption at a second active site . Glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase is prototypical of enzymes that utilize a GAT domain related to the Ntn hydrolases , whereas GMP synthetase is prototypical of enzymes that use a triad amidotransferase domain to perform the GAT function . The second active site of GMP synthetase contains a nucleotide-binding domain similar to that of ammonia-dependent NAD synthetase . It has been known for more than 30 years that Escherichia coli NAD synthetase differs from eukaryotic NAD synthetases in that it cannot use glutamine as an ammonia source . Although yeast  and some prokaryotic NAD synthetases  are glutamine dependent, they do not contain an Ntn or triad GAT domain. The glutamine-dependent NAD synthetase from Mycobacterium tuberculosis, however, contains an amino-terminal domain  not present in the E. coli enzyme . After the discovery that the multiprotein Bacillus glutamyl-tRNAGIn amidotransferase contains yet a third type of GAT activity  related to the amidase signature family , it was hypothesized that the amino terminus of the prokaryotic glutamine-dependent NAD synthetase is related to the amidase signature family .
In contrast, we find that the amino terminus of prokaryotic glutamine-dependent NAD synthetase and the amino-terminal domains of all eukaryotic NAD synthetases are branches 7 and 8 of the nitrilase superfamily, respectively. We deduce that branch 7 and 8 nitrilase-related domains have substrate specificity as glutamine amidases, and that branch 7 and 8 enzymes utilize these novel GAT domains to confer glutamine dependence to the associated carboxy-terminal NAD synthetase domains. We therefore expect to find that the presence of branch 7 nitrilase-related domains will correlate with the ability of purified prokaryotic NAD synthetases to use glutamine, and we expect that the glutamine dependence of prokaryotic and eukaryotic glutamine-dependent NAD synthetases will depend on nitrilase-homologous active-site residues. If this is confirmed, branch 7 and 8 nitrilase domains will constitute the fourth independent type of GAT domain to participate in coupled amino-transfer reactions.
As we have discussed, most branches of the nitrilase superfamily do not contain nitrilases but rather amide-hydrolyzing or amide-condensing enzymes. Although activation of water to attack planar intermediates is expected to be shared by all enzymatically active members of the superfamily, the biochemical basis for nitrile versus amide attack within the nitrilase superfamily is not yet understood. Biotinidases, branch 4 of the nitrilase superfamily, are amidases specific for hydrolysis of biotinamides such as biocytin to biotin plus lysine . For this branch, leaving group specificity allows biotinylated peptides, biocytin, simple biotinamide and biotin esters to be substrates . As alcohols are better leaving groups than amines, it would not be surprising if other members of the nitrilase superfamily have a biological function as esterases. Although no member of the nitrilase superfamily has been reported to have protease activity, members of branches 3 and 4 act on sidechains of polypeptides and members of branch 9 perform a condensation to polypeptide amino termini. Because branch 12 enzymes are fused to a probable amino-terminal acetyltransferase, they may have protein substrates as well. Protease activities may remain to be discovered in the superfamily. The enzyme activities of the nitrilase superfamily are summarized in Table 1.
Branches of the nitrilase superfamily
Branch 1: nitrilase
Members of the nitrilase branch (EC 126.96.36.199) are found in plants, animals (C. elegans), fungi (Saccharomyces cerevisiae's frequently inactivated NIT1 gene), and many types of bacteria. The best evidence that nitrilase functions in vivo to convert indoleacetonitrile to the plant growth factor indole-3-acetic acid (auxin) comes from Arabidopsis, in which it was shown that recessive mutations in a nitrilase gene resulted in reduced sensitivity to the auxin-like effects of indoleacetonitrile and that overexpression of a nitrilase caused increased sensitivity to indoleacetonitrile . Bacterial nitrilases are often exploited for biochemical syntheses and for environmental remediation . It is not clear whether bacterial nitrilases primarily function in ecological relationships with plants or whether they benefit isolated microbes.
Branch 2: aliphatic amidase
Aliphatic amidases (EC 188.8.131.52) [3,4] comprise a small branch of nearly identical proteins found in Pseudomonas, Bacillus, Brevibacteria and Helicobacteria. They hydrolyze substrates such as the carboxamide sidechains of glutamine and asparagine utilizing the conserved cysteine within the nitrilase superfamily.
Branch 3: amino-terminal amidase
The N-end rule is a means by which the rates of ubiquitin-dependent protein degradation is regulated. The S. cerevisiae Nta1 protein deaminates amino-terminal asparagine and glutamine residues to aspartate and glutamate, which lead to more rapid rates of protein turnover . Nta1 has fungal homologs but mammalian amino-terminal amidases appear to be unrelated.
Branch 4: biotinidase
Biotinidases (EC 184.108.40.206) utilize specific amidase/esterase activity to release biotin from biotinamide, biotin-lysine and biotin-peptide conjugates and biotin methylester . Biotinidase deficiency can result in an inability to recycle biotin that is manifested in neurological and cutaneous abnormalities in humans . Biotinidases are secreted into serum and have a unique, conserved carboxy-terminal domain. Vanins  and GPI-80  are members of the biotinidase branch that contain a similar carboxy-terminal domain containing, in addition, a GPI anchor and are involved in T-cell thymic homing and neutrophil adherence and migration. One member of this branch contains repeated nitrilase-related domains. Recently, porcine panthetheinase (EC 3.5.1.-), an amidase that converts pantetheine to panthothenate plus cysteamine in the dissimilative pathway of CoA, was sequenced and found to be nearly identical to vanins . Although the biologically important substrate of vanins remains unproven, sequence and enzymatic similarity with biotinidases suggest that an amine molecule at least the size of an amino acid (that is, bigger than ammonia) may be the leaving group. Branch 4 enzymes are the only amidases in the nitrilase superfamily known to prefer secondary amine substrates of the form R-C=O(NHR') as opposed to simple acid amides. An extensive archive of vanins, including 118 expressed sequence tag (EST) sequences is available [40,41].
Branch 5: β-ureidopropionase
The β-ureidopropionases (EC 220.127.116.11) are enzymes involved in the catabolism of pyrimidine bases and the production of β-alanine . Substrates of this enzyme are of the carbamylase type (see Figure 1c) and the amine product is usually a non-standard amino acid.
Branch 6: carbamylase
A variety of bacteria express hydrolases specific for the decarbamylation of D-amino acids. These enzymes have been exploited in the production of semisynthetic β-lactam antibiotics  and are now represented by the structure of the Agrobacterium enzyme .
Branches 7 and 8: glutamine-dependent NAD synthetase
As discussed earlier, the presence of a nitrilase-related domain appears to correlate with the ability of bacterial NAD synthetase (EC 18.104.22.168) to utilize glutamine as an ammonia source. Eukaryotic NAD synthetases always contain this novel, putative GAT domain and exhibit glutamine dependence. Substrate specificity of nitrilase-related proteins as glutamine amidases is not surprising given the specificity of the branch 2 and 3 enzymes. It remains to be seen how glutamine-dependent NAD synthetase may channel ammonia from the nitrilase-related active site to the NAD active site.
Branch 9: apolipoprotein N-acyltransferase
The modification and processing of Braun's lipoprotein, a major component of the outer membrane of E. coli, has been studied for decades . Defects in this post-translational modification pathway are associated with copper sensitivity . The apolipoprotein becomes proteolized, exposing an amino-terminal cysteine. After the cysteine is modified by diacylglycerol, branch 9 enzymes condense a fatty acid to the amino terminus of the modified cysteine residue.
Branch 10: Nit
Nit was originally identified as an approximately 300 amino acid amino-terminal extension on fly and worm homologs  of the human  and murine  Fhit tumor suppressor protein. Nit homologs are found in organisms with Fhit homologs  and, in the mouse, Nit1 and Fhit mRNA levels are highly correlated in seven of eight tissues examined . Satisfaction of these criteria suggested that NitFhit is a Rosetta Stone protein, whose fusion might decode a previously unsuspected interaction between the proteins [18,19]. As Fhit is part of a cell-death pathway that is not clearly connected to known apoptotic players [49,50], identification of Nit as a Fhit-interacting protein was welcomed. The Fhit active site of NitFhit has been characterized and the structure of worm NitFhit has been elucidated , but the Nit substrate, cell biology and relationship to tumor suppression are not known.
The most striking feature of the Nit-Fhit interaction apparent from the crystal structure of the worm protein is that the complex assembles with a central Nit tetramer binding two Fhit dimers . The carboxy-terminal β strands of Nit-conserved polypeptide sequences exit the compact Nit tetramer domain and physically interact with Fhit dimers. Fhit dimers are bound in a way that allows them to expose diadenosine polyphosphate-binding sites opposite from the Nit interaction surface . Futhermore, the nucleotide kinetics of NitFhit active sites  were extremely similar to those of human Fhit dimers in the absence of Nit .
Concord between the phylogenetic profiles  of Fhit and Nit breaks down slightly with the discovery of Nit-related sequences in a small number of prokaryotes that have no Fhit homolog (see the Additional data file). The idea that nitrilase-related proteins spread from animals and plants to prokaryotes is, however, supported by the animal-associated ecology of these microbes.
Branches 11 and 12 contain distinct similarity groups with no characterized member. Branch 12 may contain Rosetta Stone [18,19] proteins in that a distinctive nitrilase-related domain is found fused to an amino-terminal domain of approximately 210 amino acids. The branch-12-associated domain is related to the RimI  superfamily of amino-terminal acetyltransferases, suggesting that branch 12 enzymes are involved in post-translational modifications. Branch 13 contains uncharacterized, nonfused nitrilase-related proteins that are difficult to place in a distinct similarity group.
On the basis of newly obtained structures of nitrilase-related proteins and the available literature, we have provided a classification of all available nitrilase-related sequences. Every activity appears to work through a thiol acylenzyme intermediate and depend on a novel Glu-Lys-Cys catalytic triad. No activity forms or hydrolyzes a peptide bond, yet several affect post-translational modifications of lysine or carboxyamide sidechains or polypeptide amino termini. Other activities are involved in natural product biosynthesis and other metabolic pathways. Activities on amide substrates are found in at least eight branches of the superfamily. Activity on nitrile substrates has only been found in one branch. Membership in branches, based on BLAST E-value and structure-based signature sequence analysis, appears to correlate well with distinct substrate specificity and biological activities in all branches for which experimental data are available. Fusions between nitrilase-related domains and other conserved sequences are extremely common in the nitrilase superfamily. Fusions with NAD synthetase domains are here interpreted as solving a 30 year old problem: two branches of the nitrilase superfamily are posited to be novel GAT domains that account for the glutamine dependence of some bacterial and all eukaryotic NAD synthetases.
The following additional data file is available in HTML format: links and BLAST searches for the 176 sequences in the 13-branch classification system of the nitrilase superfamily. The additional data file can be accessed from http://genomebiology.com/content/supplementary/gb-2001-2-1-reviews0001-s1.htm
We thank Janet L. Smith for helpful comments. Work was supported by National Cancer Institute grant P01CA77738.
- Harper DB: Characterization of a nitrilase from Nocardia sp. (Rhodochrous group) N.C.I.B. 11215, using p-hydroxy-benzonitrile as sole carbon source. Int J Biochem. 1985, 17: 677-683. 10.1016/0020-711X(85)90364-7.View ArticleGoogle Scholar
- Harper DB: Microbial metabolism of aromatic nitriles. Biochem J. 1977, 165: 309-319.View ArticleGoogle Scholar
- Ambler RP, Auffret AD, Clarke PH: The amino acid sequence of the aliphatic amidase from Pseudomonas aeruginosa. FEBS Lett. 1987, 215: 285-290. 10.1016/0014-5793(87)80163-1.View ArticleGoogle Scholar
- Novo C, Tata R, Clemente A, Brown PR: Pseudomonas aeruginosa aliphatic amidase is related to the nitrilase/cyanide hydratase enzyme family and Cys166 is predicted to be the active site nucleophile of the catalytic mechanism. FEBS Lett. 1995, 367: 275-279. 10.1016/0014-5793(95)00585-W.View ArticleGoogle Scholar
- Stevenson DE, Feng R, Storer AC: Detection of covalent enzyme-substrate complexes of nitrilase by ion-spray mass spectroscopy. FEBS Lett. 1990, 277: 112-114. 10.1016/0014-5793(90)80821-Y.View ArticleGoogle Scholar
- Bork P, Koonin EV: A new family of carbon-nitrogen hydrolases. Protein Sci. 1994, 3: 1344-1346.View ArticleGoogle Scholar
- Spencer RL, Preiss J: Biosynthesis of diphosphopyridine nucleotide. The purification and the properties of diphospyridine nucleotide synthetase from Escherichia coli b. J Biol Chem. 1967, 242: 385-392.Google Scholar
- Yu CK, Dietrich LS: Purification and properties of yeast nicotinamide adenine dinucleotide synthetase. J Biol Chem. 1972, 247: 4794-4802.Google Scholar
- Zalkin H: NAD synthetase. Methods Enzymol. 1985, 113: 297-302.View ArticleGoogle Scholar
- Zalkin H, Smith JL: Enzymes utilizing glutamine as an amide donor. Advances in Enzymology and Related Areas of Molecular Biology. 1998, 72: 87-144.Google Scholar
- Curnow AW, Kw H, Yuan R, Si K, Martins O, Winkler W, Henkin TM, Soll D: Glu-tRNAGln amidotransferase: a novel heterotrimeric enzyme required for correct decoding of glutamine codons during translation. Proc Natl Acad Sci USA. 1997, 94: 11819-11826. 10.1073/pnas.94.22.11819.View ArticleGoogle Scholar
- Pace HC, Hodawadekar SC, Draganescu A, Huang J, Bieganowski P, Pekarsky Y, Croce CM, Brenner C: Crystal structure of the worm NitFhit Rosetta Stone protein reveals a Nit tetramer binding two Fhit dimers. Curr Biol. 2000, 10: 907-917. 10.1016/S0960-9822(00)00621-7.View ArticleGoogle Scholar
- Nakai T, Hasegawa T, Yamashita E, Yamamoto M, Kumasaka T, Ueki T, Nanba H, Ikenaka Y, Takahashi S, Sato M, et al: Crystal structure of N-carbamyl-D-amino acid amidohydrolase with a novel catalytic framework common to amidohydrolases. Structure. 2000, 8: 729-737. 10.1016/S0969-2126(00)00160-X.View ArticleGoogle Scholar
- Huang W, Jia J, Cummings J, Nelson M, Schneider G, Lindqvist Y: Crystal structure of nitrile hydratase reveals a novel iron centre in a novel fold. Structure. 1997, 5: 691-699.View ArticleGoogle Scholar
- Patricelli MP, Cravatt BF: Clarifying the catalytic roles of conserved residues in the amidase signature family. J Biol Chem. 2000, 275: 19177-19184. 10.1074/jbc.M001607200.View ArticleGoogle Scholar
- Rawlings ND, Barrett AJ: MEROPS: the peptidase database. Nucleic Acids Res. 2000, 28: 323-325. 10.1093/nar/28.1.323.View ArticleGoogle Scholar
- Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.View ArticleGoogle Scholar
- Marcotte EM, Pellegrini M, Ng HL, Rice DW, Yeates TO, Eisenberg D: Detecting protein function and protein-protein interactions from genome sequences. Science. 1999, 285: 751-753. 10.1126/science.285.5428.751.View ArticleGoogle Scholar
- Marcotte E, Pellegrini M, Thompson M, Yeates T, Eisenberg D: A combined algorithm for genome-wide prediction of protein function. Nature. 1999, 402: 83-86. 10.1038/47048.View ArticleGoogle Scholar
- Smith JL, Zaluzec EJ, Wery JP, Niu L, Switzer RL, Zalkin H, Satow Y: Structure of the allosteric regulatory enzyme of purine biosynthesis. Science. 1994, 264: 1427-1433.View ArticleGoogle Scholar
- Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL: The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families. Nat Struct Biol. 1996, 3: 74-86.View ArticleGoogle Scholar
- Rizzi M, Nessi C, Mattevi A, Coda A, Bolognesi M, Galizzi A: Crystal structure of NH3-dependent NAD+ synthetase from Bacillus subtilis. EMBO J. 1996, 15: 5125-5134.Google Scholar
- Cantoni R, Branzoni M, Labo M, Rizzi M, Riccardi G: The MTCY428.08 gene of Mycobacterium tuberculosis codes for NAD+ synthetase. J Bacteriol. 1998, 180: 3218-3221.Google Scholar
- Willison JC, Tissot G: The Escherichia coli efg gene and the Rhodobacter capsulatus adgA gene code for NH3-dependent NAD synthetase. J Bacteriol. 1994, 176: 3400-3402.Google Scholar
- Stevenson DE, Feng R, Dumas F, Groleau D, Mihoc A, Storer AC: Mechanistic and structural studies on Rhodococcus ATCC 39484 nitrilase. Biotechol Appl Biochem. 1992, 15: 283-302.Google Scholar
- Stalker DM, Malyj LD, McBride KE: Purification and properties of a nitrilase specific for the herbicide bromoxynil and corresponding nucleotide sequence analysis of the bxn gene. J Biol Chem. 1988, 263: 6310-6314.Google Scholar
- Kobayashi M, Nagasawa T, Yamada H: Nitrilase of Rhodococcus rhodochrous J1, Purification and characterization. Eur J Biochem. 1989, 182: 349-356.View ArticleGoogle Scholar
- Schmidt RC, Muller A, Hain R, Bartling D, Weiler EW: Transgenic tobacco plants expressing the Arabidopsis thaliana nitrilase II enzyme. Plant J. 1996, 9: 683-691.View ArticleGoogle Scholar
- Wang P, VanEtten HD: Cloning and properties of a cyanide hydratase gene from the phytopathogenic fungus Gloeocercospora sorghi. Biochem Biophys Res Commun. 1992, 187: 1048-1054.View ArticleGoogle Scholar
- Cluness MJ, Turner PD, Clements E, Brown DT, O'Reilly C: Purification and properties of cyanide hydratase from Fusarium lateritium and analysis of the corresponding chy1 gene. J Gen Microbiol. 1993, 139: 1807-1815.View ArticleGoogle Scholar
- Hymes J, Wolf B: Biotinidase and its roles in biotin metabolism. Clinica Chimica Acta. 1996, 255: 1-11. 10.1016/0009-8981(96)06396-6.View ArticleGoogle Scholar
- Normanly J, Grisafi P, Fink GR, Bartel B: Arabidopsis mutants resistant to the auxin effects of indole-3-acetonitrile are defective in the nitrilase encoded by the NIT1 gene. Plant Cell. 1997, 9: 1781-1790. 10.1105/tpc.9.10.1781.View ArticleGoogle Scholar
- Cowan D, Cramp R, Pereira R, Graham D, Almatawah Q: Biochemistry and biotechnology of mesophilic and thermophilic nitrile metabolizing enzymes. Extremophiles. 1998, 2: 207-216. 10.1007/s007920050062.View ArticleGoogle Scholar
- Baker RT, Varshavsky A: Yeast N-terminal amidase. A new enzyme and component of the N-end rule pathway. J Biol Chem. 1995, 270: 12065-12074. 10.1074/jbc.270.20.12065.View ArticleGoogle Scholar
- Cole H, Reynolds TR, Lockyer JM, Buck GA, Denson T, Spence JE, Hymes , Wolf B: Human serum biotinase: cDNA cloning, sequence, and characterization. J Biol Chem. 1994, 269: 6566-6570.Google Scholar
- Pomponio RJ, Hymes J, Reynolds TR, Meyers GA, Fleischhauer K, Buck GA, Wolf B: Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. Pediatric Research. 1997, 42: 840-848.View ArticleGoogle Scholar
- Aurrand-Lions M, Galland F, Bazin H, Zakharyev VM, Imhof BA, Naquet P: Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing. Immunity. 1996, 5: 391-405.View ArticleGoogle Scholar
- Suzuki K, Watanabe T, Sakurai S, Ohtake K, Kinoshita T, Araki A, Fujita T, Takei H, Takeda Y, Sato Y, Yamashita T, Araki Y, Sendo F: A novel glycosylphosphatidyl inositol-anchored protein on human leukocytes: a possible role for regulation of neutrophil adherence and migration. J Immunol. 1999, 162: 4277-4284.Google Scholar
- Maras B, Barra D, Dupre S, Pitari G: Is pantetheinase the actual identity of mouse and human vanin-1 proteins?. FEBS Lett. 1999, 461: 149-152. 10.1016/S0014-5793(99)01439-8.View ArticleGoogle Scholar
- Granjeaud S, Naquet P, Galland F: An ESTs description of the new Vanin gene family conserved from fly to human. Immunogenetics. 1999, 49: 964-972. 10.1007/s002510050580.View ArticleGoogle Scholar
- Vanin project. [http://tagc.univ-mrs.fr/pub/vanin]
- Kvalnes-Krick KL, Traut TW: Cloning, sequencing, and expression of a cDNA encoding beta-alanine synthase from rat liver. J Biol Chem. 1993, 268: 5686-5693.Google Scholar
- Louwrier A, Knowles CJ: The aim of industrial enzymic amoxycillin production: characterization of a novel carbamoylase enzyme in the form of a crude, cell-free extract. Biotechnol Appl Biochem. 1997, 25: 143-149.Google Scholar
- Tokunaga M, Tokunaga H, Wu HC: Post-translational modification and processing of Eschericia coli prolipoprotein in vitro. Proc Natl Acad Sci USA. 1982, 79: 2255-2259.View ArticleGoogle Scholar
- Rogers SD, Bhave MR, Mercer JFB, Camakaris J, Lee BTO: Cloning and characterization of cutE, a gene involved in copper transport in Escherichia coli. J Bacteriol. 1991, 173: 6742-6748.Google Scholar
- Pekarsky Y, Campiglio M, Siprashvili Z, Druck T, Sedkov Y, Tillib S, Draganescu A, Wermuth P, Rothman JH, Huebner K, Buchberg AM, Mazo A, Brenner C, Croce CM: Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans. Proc Natl Acad Sci USA. 1998, 95: 8744-8749. 10.1073/pnas.95.15.8744.View ArticleGoogle Scholar
- Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, et al: The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell. 1996, 84: 587-597.View ArticleGoogle Scholar
- Fong LYY, Fidanza V, Zanesi N, Lock LF, Siracusa LD, Mancini R, Siprashvili Z, Ottey M, Martin SE, Dolsky R, Druck T, McCue PA, Croce CM, Huebner K: Muir-Torre-like syndrome in FHIT deficient mice. Proc Natl Acad Sci USA. 2000, 97: 4742-4747. 10.1073/pnas.080063497.View ArticleGoogle Scholar
- Sard L, Accornero P, Tornielli S, Delia D, Bunone G, Campiglio M, Colombo MP, Gramegna M, Croce CM, Pierotti MA, et al: The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control. Proc Natl Acad Sci USA. 1999, 96: 8489-8492. 10.1073/pnas.96.15.8489.View ArticleGoogle Scholar
- Ji L, Fang B, Yeh N, Fong K, Minna JD, Roth JA: Induction of apoptosis and inhibition of tumorigenicity and tumor growth by adenovirus vector-mediated fragile histidine triad (FHIT) gene overexpression. Cancer Res. 1999, 59: 3333-3339.Google Scholar
- Draganescu A, Hodawadekar SC, Gee KR, Brenner C: Fhit-nucleotide specificity probed with novel fluorescent and fluorigenic substrates. J Biol Chem. 2000, 275: 4555-4560. 10.1074/jbc.275.7.4555.View ArticleGoogle Scholar
- Pellegrini M, Marcotte EM, Thompson MJ, Eisenberg D, Yeates TO: Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci USA. 1999, 96: 4285-4288. 10.1073/pnas.96.8.4285.View ArticleGoogle Scholar
- Yoshikawa A, Isono S, Sheback A, Isono K: Cloning and nucleotide sequencing of the genes rimI and rimJ which encode enzymes acetylating ribosomal proteins S18 and S5 of Esherichia coli K12. Mol Gen Genet. 1987, 209: 481-488.View ArticleGoogle Scholar
- Corpet F: Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 1988, 16: 10881-10890.View ArticleGoogle Scholar