cd00317, cyclophilin, cyclophilin: cyclophilin-type peptidylprolyl cis- trans isomerases. This family contains eukaryotic, bacterial and archeal proteins which exhibit a peptidylprolyl cis- trans isomerases activity (PPIase, Rotamase) and in addition bind the immunosuppressive drug cyclosporin (CsA). Immunosuppression in vertebrates is believed to be the result of the cyclophilin A-cyclosporin protein drug complex binding to and inhibiting the protein-phosphatase calcineurin. PPIase is an enzyme which accelerates protein folding by catalyzing the cis-trans isomerization of the peptide bonds preceding proline residues. Cyclophilins are a diverse family in terms of function and have been implicated in protein folding processes which depend on catalytic /chaperone-like activities. This group contains human cyclophilin 40, a co-chaperone of the hsp90 chaperone system; human cyclophilin A, a chaperone in the HIV-1 infectious process and; human cyclophilin H, a component of the U4/U6 snRNP, whose isomerization or chaperoning activities may play a role in RNA splicing. .
cd07249, MMCE, Methylmalonyl-CoA epimerase (MMCE). MMCE, also called methylmalonyl-CoA racemase (EC 5.1.99.1) interconverts (2R)-methylmalonyl-CoA and (2S)-methylmalonyl-CoA. MMCE has been found in bacteria, archaea, and in animals. In eukaryotes, MMCE is an essential enzyme in a pathway that converts propionyl-CoA to succinyl-CoA, and is important in the breakdown of odd-chain length fatty acids, branched-chain amino acids, and other metabolites. In bacteria, MMCE participates in the reverse pathway for propionate fermentation, glyoxylate regeneration, and the biosynthesis of polyketide antibiotics. MMCE is closely related to glyoxalase I and type I extradiol dioxygenases.
pfam09754, PAC2, PAC2 family. This PAC2 (Proteasome assembly chaperone) family of proteins is found in bacteria, archaea and eukaryotes. Proteins in this family are typically between 247 and 307 amino acids in length. These proteins function as a chaperone for the 26S proteasome. The 26S proteasome mediates ubiquitin-dependent proteolysis in eukaryotic cells. A number of studies including very recent ones have revealed that assembly of its 20S catalytic core particle is an ordered process that involves several conserved proteasome assembly chaperones (PACs). Two heterodimeric chaperones, PAC1-PAC2 and PAC3-PAC4, promote the assembly of rings composed of seven alpha subunits.
TIGR01995, beta-glucosides_PTS_EIIBCA, PTS system, beta-glucoside-specific IIABC component. This model represents a family of PTS enzyme II proteins in which all three domains are found in the same polypeptide chain and which appear to have a broad specificity for beta-glucosides including salicin (beta-D-glucose-1-salicylate) and arbutin (Hydroquinone-O-beta-D-glucopyranoside). These are distinct from the closely related sucrose-specific and trehalose-specific PTS transporters.
TIGR02009, Hypothetical_protein_Rv3400/MT3508/Mb3433., beta-phosphoglucomutase family hydrolase. This subfamily model groups together three clades: the characterized beta-phosphoglucomutases (including those from E.coli, B.subtilus and L.lactis, TIGR01990), a clade of putative bPGM's from mycobacteria and a clade including the uncharacterized E.coli and H.influenzae yqaB genes which may prove to be beta-mutases of a related 1-phosphosugar. All of these are members of the larger Haloacid dehalogenase (HAD) subfamily IA and include the "variant 3" glu-asp version of the third conserved HAD domain (TIGR01509).
cd02883, Nudix_Hydrolase, Nudix hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes 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. Members of this family are recognized by a highly conserved 23-residue nudix motif (GX5EX7REUXEEXGU, where U = I, L or V), which forms a structural motif that functions as a metal binding and catalytic site. Substrates of nudix hydrolase 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 and "house-cleaning" enzymes. Substrate specificity is used to define child 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. This superfamily consists of at least nine families: IPP (isopentenyl diphosphate) isomerase, ADP ribose pyrophosphatase, mutT pyrophosphohydrolase, coenzyme-A pyrophosphatase, MTH1-7,8-dihydro-8-oxoguanine-triphosphatase, diadenosine tetraphosphate hydrolase, NADH pyrophosphatase, GDP-mannose hydrolase and the c-terminal portion of the mutY adenine glycosylase.
cd09008, MTAN, 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidases. This subfamily includes both bacterial and plant 5'-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidases (MTANs): bacterial MTANs show comparable efficiency in hydrolyzing MTA and SAH, while plant enzymes are highly specific for MTA and are unable to metabolize SAH or show significantly reduced activity towards SAH. MTAN is involved in methionine and S-adenosyl-methionine recycling, polyamine biosynthesis, and bacterial quorum sensing. This subfamily belongs to the nucleoside phosphorylase-I (NP-I) family, whose members accept a range of purine nucleosides as well as the pyrimidine nucleoside uridine. The NP-1 family includes phosphorolytic nucleosidases, such as purine nucleoside phosphorylase (PNPs, EC. 2.4.2.1), uridine phosphorylase (UP, EC 2.4.2.3), and 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP, EC 2.4.2.28), and hydrolytic nucleosidases, such as AMP nucleosidase (AMN, EC 3.2.2.4), and 5'-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidase (MTAN, EC 3.2.2.16). The NP-I family is distinct from nucleoside phosphorylase-II, which belongs to a different structural family.
cd10170, HSP70_NBD, Nucleotide-binding domain of the HSP70 family. HSP70 (70-kDa heat shock protein) family chaperones assist in protein folding and assembly and can direct incompetent "client" proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. HSP70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). Some HSP70 family members are not chaperones but instead, function as NEFs to remove ADP from their HSP70 chaperone partners during the ATP hydrolysis cycle, some may function as both chaperones and NEFs.
