cd01949, GGDEF, Diguanylate-cyclase (DGC) or GGDEF domain. Diguanylate-cyclase (DGC) or GGDEF domain: Originally named after a conserved residue pattern, and initially described as a domain of unknown function 1 (DUF1). This domain is widely present in bacteria, linked to a wide range of non-homologous domains in a variety of cell signaling proteins. The domain shows homology to the adenylyl cyclase catalytic domain. This correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. Together with the EAL domain, GGDEF might be involved in regulating cell surface adhesion in bacteria.
cd02933, OYE_like_FMN, Old yellow enzyme (OYE)-like FMN binding domain. OYE was the first flavin-dependent enzyme identified, however its true physiological role remains elusive to this day. Each monomer of OYE contains FMN as a non-covalently bound cofactor, uses NADPH as a reducing agent with oxygens, quinones, and alpha,beta-unsaturated aldehydes and ketones, and can act as electron acceptors in the catalytic reaction. Members of OYE family include 12-oxophytodienoate reductase, pentaerythritol tetranitrate reductase, morphinone reductase, and related enzymes.
cd16153, sulfatase_like, uncharacterized sulfatase subfamily. Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases.
cd05283, CAD1, Cinnamyl alcohol dehydrogenases (CAD). Cinnamyl alcohol dehydrogenases (CAD), members of the medium chain dehydrogenase/reductase family, reduce cinnamaldehydes to cinnamyl alcohols in the last step of monolignal metabolism in plant cells walls. CAD binds 2 zinc ions and is NADPH- dependent. CAD family members are also found in non-plant species, e.g. in yeast where they have an aldehyde reductase activity. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES. The MDR group contains a host of activities, including the founding alcohol dehydrogenase (ADH), quinone reductase, sorbitol dehydrogenase, formaldehyde dehydrogenase, butanediol DH, ketose reductase, cinnamyl reductase, and numerous others. The zinc-dependent alcohol dehydrogenases (ADHs) catalyze the NAD(P)(H)-dependent interconversion of alcohols to aldehydes or ketones. Active site zinc has a catalytic role, while structural zinc aids in stability. ADH-like proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and generally have 2 tightly bound zinc atoms per subunit. The active site zinc is coordinated by a histidine, two cysteines, and a water molecule. The second zinc seems to play a structural role, affects subunit interactions, and is typically coordinated by 4 cysteines.
cd01347, ligand_gated_channel, TonB dependent/Ligand-Gated channels are created by a monomeric 22 strand (22,24) anti-parallel beta-barrel. Ligands apparently bind to the large extracellular loops. The N-terminal 150-200 residues form a plug from the periplasmic end of barrel. Energy (proton-motive force) and TonB-dependent conformational alteration of channel (parts of plug, and loops 7 and 8) allow passage of ligand. FepA residues 12-18 form the TonB box, which mediates the interaction with the TonB-containing inner membrane complex. TonB preferentially interacts with ligand-bound receptors. Transport thru the channel may resemble passage thru an air lock. In this model, ligand binding leads to closure of the extracellular end of pore, then a TonB-mediated signal facillitates opening of the interior side of pore, deforming the N-terminal plug and allowing passage of the ligand to the periplasm. Such a mechanism would prevent the free diffusion of small molecules thru the pore.
cd17324, MFS_NepI_like, Purine ribonucleoside efflux pump NepI and similar transporters of the Major Facilitator Superfamily. This family is composed of purine efflux pumps such as Escherichia coli NepI and Bacillus subtilis PbuE, sugar efflux transporters such as Corynebacterium glutamicum arabinose efflux permease, multidrug resistance (MDR) transporters such as Streptomyces lividans chloramphenicol resistance protein (CmlR), and similar proteins. NepI and PbuE are involved in the efflux of purine ribonucleosides such as guanosine, adenosine and inosine, as well as purine bases like guanine, adenine, and hypoxanthine, and purine base analogs. They play a role in the maintenance of cellular purine base pools, as well as in protecting the cells and conferring resistance against toxic purine base analogs such as 6-mercaptopurine. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. The NepI-like family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
cd08942, RhlG_SDR_c, RhlG and related beta-ketoacyl reductases, classical (c) SDRs. Pseudomonas aeruginosa RhlG is an SDR-family beta-ketoacyl reductase involved in Rhamnolipid biosynthesis. RhlG is similar to but distinct from the FabG family of beta-ketoacyl-acyl carrier protein (ACP) of type II fatty acid synthesis. RhlG and related proteins are classical SDRs, with a canonical active site tetrad and glycine-rich NAD(P)-binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.
TIGR02334, conserved_hypothetical_protein, probable AcnD-accessory protein PrpF. The 2-methylcitrate cycle is one of at least five degradation pathways for propionate via propionyl-CoA. Degradation of propionate toward pyruvate consumes oxaloacetate and releases succinate. Oxidation of succinate back into oxaloacetate by the TCA cycle makes the 2-methylcitrate pathway a cycle. This family consists of PrpF, an incompletely characterized protein that appears to be an essential accessory protein for the Fe/S-dependent 2-methylisocitrate dehydratase AcnD (TIGR02333). This protein is related to but distinct from FldA (part of pfam04303), a putative fluorene degradation protein of Sphingomonas sp. LB126. [Energy metabolism, Fermentation].
pfam11169, DUF2956, Protein of unknown function (DUF2956). This family of proteins with unknown function appears to be restricted to Gammaproteobacteria.
TIGR01782, TonB-dependent_receptor, TonB-dependent receptor. This model represents a family of TonB-dependent outer-membrane receptors which are found mainly in Xanthomonas and Caulobacter. These appear to represent the expansion of a paralogous family in that the 22 X. axonopodis (21 in X. campestris) and 18 C. crescentus sequences are more closely related to each other than any of the many TonB-dependent receptors found in other species. In fact, the Crescentus and Xanthomonas sequences are inseparable on a phylogenetic tree using a PAM-weighted neighbor-joining method, indicating that one of the two genuses may have acquired this set of receptors from the other. The mechanism by which this family is shared between Xanthomonas, a gamma proteobacterial plant pathogen and Caulobacter, an alpha proteobacterial aquatic organism is unclear. [Transport and binding proteins, Porins].
TIGR02333, 2-methyl_citrate_dehydratase_Fe-S_dependent_AcnD, 2-methylisocitrate dehydratase, Fe/S-dependent. Members of this family appear in an operon for the degradation of propionyl-CoA via 2-methylcitrate. This family is homologous to aconitases A and B and appears to act the part as 2-methylisocitrate dehydratase, the enzyme after PrpD and before PrpB. In Escherichia coli, which lacks a member of this family, 2-methylisocitrate dehydratase activity was traced to aconitase B (TIGR00117) ().
sd00045, ANK, ankyrin repeats. Ankyrin repeats are one of the most abundant repeat motifs, and generally function as scaffolds for protein-protein interactions in processes including cell cycle, transcriptional regulation, signal transduction, vesicular trafficking, and inflammatory response. Although predominantly found in eukaryotic proteins, they are also found in some bacterial and viral proteins. Less is known of their physiological roles in prokaryotes. Some bacterial ANK proteins play key roles in microbial pathogenesis by mimicking or manipulating host function(s). The pathogen Providencia alcalifaciens N-formyltransferase ankyrin repeats function in small molecule binding and allosteric control. Ankyrin-repeat proteins have been associated with a number of human diseases.
cd11477, SLC5sbd_u1, Uncharacterized bacterial solute carrier 5 subfamily; putative solute-binding domain. SLC5 (also called the sodium/glucose cotransporter family or solute sodium symporter family) is a family of proteins that co-transports Na+ with sugars, amino acids, inorganic ions or vitamins. Prokaryotic members of this family include Vibrio parahaemolyticus glucose/galactose (vSGLT), and Escherichia coli proline (PutP) and pantothenate (PutF) cotransporters. One member of the SLC5 family, human SGLT3, has been characterized as a glucose sensor and not a transporter. This subfamily belongs to the solute carrier 5 (SLC5) transporter family.
cd04276, ZnMc_MMP_like_2, Zinc-dependent metalloprotease; MMP_like sub-family 2. A group of bacterial metalloproteinase domains similar to matrix metalloproteinases and astacin.
cd00249, AGE, AGE domain; N-acyl-D-glucosamine 2-epimerase domain; Responsible for intermediate epimerization during biosynthesis of N-acetylneuraminic acid. Catalytic mechanism is believed to be via nucleotide elimination and readdition and is ATP modulated. AGE is structurally and mechanistically distinct from the other four types of epimerases. The AGE domain monomer is composed of an alpha(6)/alpha(6)-barrel, the structure of which is also found in glucoamylase and cellulase. The active form is a homodimer. The alignment also contains subtype III mannose 6-phosphate isomerases.
pfam01663, Phosphodiest, Type I phosphodiesterase / nucleotide pyrophosphatase. This family consists of phosphodiesterases, including human plasma-cell membrane glycoprotein PC-1 / alkaline phosphodiesterase i / nucleotide pyrophosphatase (nppase). These enzymes catalyze the cleavage of phosphodiester and phosphosulfate bonds in NAD, deoxynucleotides and nucleotide sugars. Also in this family is ATX an autotaxin, tumor cell motility-stimulating protein which exhibits type I phosphodiesterases activity. The alignment encompasses the active site. Also present with in this family is 60-kDa Ca2+-ATPase form F. odoratum.
cd04681, Nudix_Hydrolase_22, Members of the Nudix hydrolase superfamily catalyze the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and contain a highly conserved 23-residue nudix motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. Substrates of nudix hydrolases include intact and oxidatively damaged nucleoside triphosphates, dinucleoside polyphosphates, nucleotide-sugars and dinucleotide enzymes. These substrates are metabolites or cell signaling molecules that require regulation during different stages of the cell cycle or during periods of stress. In general, the role of the nudix hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance & "house-cleaning" enzymes. Substrate specificity is used to define families within the superfamily. Differences in substrate specificity are determined by the N-terminal extension or by residues in variable loop regions. Mechanistically, substrate hydrolysis occurs by a nucleophilic substitution reaction, with variation in the numbers and roles of divalent cations required.
cd08154, catalase_clade_1, Clade 1 of the heme-binding enzyme catalase. Catalase is a ubiquitous enzyme found in both prokaryotes and eukaryotes, which is involved in the protection of cells from the toxic effects of peroxides. It catalyzes the conversion of hydrogen peroxide to water and molecular oxygen. Catalases also utilize hydrogen peroxide to oxidize various substrates such as alcohol or phenols. Clade 1 catalases are found in bacteria, algae, and plants; they have a relatively small subunit size of 55 to 69 kDa, and bind a protoheme IX (heme b) group buried deep inside the structure. They appear to form tetramers. In eukaryotic cells, catalases are located in peroxisomes.
cd16146, ARS_like, uncharacterized arylsulfatase. Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases.
cd08993, GH130, Glycosyl hydrolase family 130. This subfamily contains glycosyl hydrolase family 130 (GH130) proteins, as classified by the carbohydrate-active enzymes database (CAZY), are phosphorylases and hydrolases for beta-mannosides, and include beta-1,4-mannosylglucose phosphorylase (EC 2.4.1.281), beta-1,4-mannooligosaccharide phosphorylase (EC 2.4.1.319), among others that have yet to be characterized. They possess 5-bladed beta-propeller domains similar to families 32, 43, 62, 68, 117 (GH32, GH43, GH62, GH68, GH117). GH130 enzymes are involved in the bacterial utilization of mannans or N-linked glycans. Beta-1,4-mannosylglucose phosphorylase is involved in degradation of beta-1,4-D-mannosyl-N-acetyl-D-glucosamine linkages in the core of N-glycans; it produces alpha-mannose 1-phosphate and glucose from 4-O-beta-D-mannosyl-D-glucose and inorganic phosphate, using a critical catalytic Asp as a proton donor. This family includes Ruminococcus albus 4-O-beta-D-mannosyl-D-glucose phosphorylase (RaMP1) and beta-(1,4)-mannooligosaccharide phosphorylase (RaMP2), enzymes that phosphorolyze beta-mannosidic linkages at the non-reducing ends of their substrates, and have substantially diverse substrate specificity that are determined by three loop regions.
cd00249, AGE, AGE domain; N-acyl-D-glucosamine 2-epimerase domain; Responsible for intermediate epimerization during biosynthesis of N-acetylneuraminic acid. Catalytic mechanism is believed to be via nucleotide elimination and readdition and is ATP modulated. AGE is structurally and mechanistically distinct from the other four types of epimerases. The AGE domain monomer is composed of an alpha(6)/alpha(6)-barrel, the structure of which is also found in glucoamylase and cellulase. The active form is a homodimer. The alignment also contains subtype III mannose 6-phosphate isomerases.
TIGR01782, TonB-dependent_receptor, TonB-dependent receptor. This model represents a family of TonB-dependent outer-membrane receptors which are found mainly in Xanthomonas and Caulobacter. These appear to represent the expansion of a paralogous family in that the 22 X. axonopodis (21 in X. campestris) and 18 C. crescentus sequences are more closely related to each other than any of the many TonB-dependent receptors found in other species. In fact, the Crescentus and Xanthomonas sequences are inseparable on a phylogenetic tree using a PAM-weighted neighbor-joining method, indicating that one of the two genuses may have acquired this set of receptors from the other. The mechanism by which this family is shared between Xanthomonas, a gamma proteobacterial plant pathogen and Caulobacter, an alpha proteobacterial aquatic organism is unclear. [Transport and binding proteins, Porins].
pfam04364, DNA_pol3_chi, DNA polymerase III chi subunit, HolC. The DNA polymerase III holoenzyme (EC:2.7.7.7) is the polymerase responsible for the replication of the Escherichia coli chromosome. The holoenzyme is composed of the DNA polymerase III core, the sliding clamp, and the DnaX clamp loading complex. The DnaX complex contains either either the tau or gamma product of gene dnax, complexed to delta.delta' and to chi psi. Chi forms a 1:1 heterodimer with psi. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta' allowing a functional clamp-loading complex to form at physiological subunit concentrations. Psi is responsible for the interaction with DnaX (gamma/tau), but psi is insoluble unless it is in a complex with chi.
cd14251, PL-6, Polysaccharide Lyase Family 6. Polysaccharide Lyase Family 6 is a family of beta-helical polysaccharide lyases. Members include alginate lyase (EC 4.2.2.3) and chondroitinase B (EC 4.2.2.19). Chondroitinase B is an enzyme that only cleaves the beta-(1,4)-linkage of dermatan sulfate (DS), leading to 4,5-unsaturated dermatan sulfate disaccharides as the product. DS is a highly sulfated, unbranched polysaccharide belonging to a family of glycosaminoglycans (GAGs) composed of alternating hexosamine (gluco- or galactosamine) and uronic acid (D-glucuronic or L-iduronic acid) moieties. DS contains alternating 1,4-beta-D-galactosamine (GalNac) and 1,3-alpha-L-iduronic acid units. The related chondroitin sulfate (CS) contains alternating GalNac and 1,3-beta-D-glucuronic acid units. Alginate lyases (known as either mannuronate (EC 4.2.2.3) or guluronate lyases (EC 4.2.2.11) catalyze the degradation of alginate, a copolymer of alpha-L-guluronate and its C5 epimer beta-D-mannuronate.
pfam06271, RDD, RDD family. This family of proteins contain three highly conserved amino acids: one arginine and two aspartates, hence the name of RDD family. This region contains two predicted transmembrane regions. The arginine occurs at the N-terminus of the first helix and the first aspartate occurs in the middle of this helix. The molecular function of this region is unknown. However this region may be involved in transport of an as yet unknown set of ligands (Bateman A pers. obs.).
cd01949, GGDEF, Diguanylate-cyclase (DGC) or GGDEF domain. Diguanylate-cyclase (DGC) or GGDEF domain: Originally named after a conserved residue pattern, and initially described as a domain of unknown function 1 (DUF1). This domain is widely present in bacteria, linked to a wide range of non-homologous domains in a variety of cell signaling proteins. The domain shows homology to the adenylyl cyclase catalytic domain. This correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. Together with the EAL domain, GGDEF might be involved in regulating cell surface adhesion in bacteria.
cd07262, VOC_like, uncharacterized subfamily of vicinal oxygen chelate (VOC) family. The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta.alpha.beta.beta.beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. VOC domain is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. A bound metal ion is required for protein activities for the members of this superfamily. A variety of metal ions have been found in the catalytic centers of these proteins including Fe(II), Mn(II), Zn(II), Ni(II) and Mg(II). The protein superfamily contains members with or without domain swapping. The proteins of this family share three conserved metal binding amino acids with the type I extradiol dioxygenases, which shows no domain swapping.
TIGR03696, tRNA_nuclease_WapA, RHS repeat-associated core domain. This model represents a conserved unique core sequence shared by large numbers of proteins. It is occasional in the Archaea Methanosarcina barkeri) but common in bacteria and eukaryotes. Most fall into two large classes. One class consists of long proteins in which two classes of repeats are abundant: an FG-GAP repeat (pfam01839) class, and an RHS repeat (pfam05593) or YD repeat (TIGR01643). This class includes secreted bacterial insecticidal toxins and intercellular signalling proteins such as the teneurins in animals. The other class consists of uncharacterized proteins shorter than 400 amino acids, where this core domain of about 75 amino acids tends to occur in the N-terminal half. Over twenty such proteins are found in Pseudomonas putida alone; little sequence similarity or repeat structure is found among these proteins outside the region modeled by this domain.
pfam08787, Alginate_lyase2, Alginate lyase. Alginate lyases are enzymes that degrade the linear polysaccharide alignate. They cleave the glycosidic linkage of alignate through a beta-elimination reaction. This family forms an all beta fold and is different to all alpha fold of pfam05426.
TIGR04407, LptF_YjgP, LPS export ABC transporter permease LptF. Members of this family are LptF, one of homologous, two tandem-encoded permease genes of an export ATP transporter for lipopolysaccharide (LPS) assembly in most Gram-negative bacteria. The other permease subunit is LptG (TIGR04408). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides, Transport and binding proteins, Other].
TIGR01782, TonB-dependent_receptor, TonB-dependent receptor. This model represents a family of TonB-dependent outer-membrane receptors which are found mainly in Xanthomonas and Caulobacter. These appear to represent the expansion of a paralogous family in that the 22 X. axonopodis (21 in X. campestris) and 18 C. crescentus sequences are more closely related to each other than any of the many TonB-dependent receptors found in other species. In fact, the Crescentus and Xanthomonas sequences are inseparable on a phylogenetic tree using a PAM-weighted neighbor-joining method, indicating that one of the two genuses may have acquired this set of receptors from the other. The mechanism by which this family is shared between Xanthomonas, a gamma proteobacterial plant pathogen and Caulobacter, an alpha proteobacterial aquatic organism is unclear. [Transport and binding proteins, Porins].
