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Listeriolysin O (aka LLO) is a hemolysin produced by Listeria monocytogenes bacteria, the pathogen responsible for causing listeriosis. The toxin may be regarded as a virulence factor, since it is crucial for the virulence of L. monocytogenes. LLO is a single polypeptide protein encoded by the hlyA gene and composed of 529 residues. LLO is a thiol-activated cholesterol-dependent pore forming toxin protein; therefore, it is activated by reducing agents and inhibited by oxidizing agents. Still, LLO differs from other thiol-activated toxins, as its cytolytic activity is maximized at a pH of 5.5. Inside the acidic phagosomes (average pH ~ 5.9) of cells that have phagocytosed L. monocytogenes, LLO is selectively activated by maximizing activity at a pH of 5.5. Following the phagosome lysis by LLO, the bacterium breaks out into the cytosol, where it is able to grow intracellularly, and the toxin has reduced activity in the more basic cytosol. Thus, LLO permits L. monocytogenes to break out from the phagosomes into the cytosol without harming the plasma membrane of the infected cell, which allows the bacteria to live intracellularly, where they are sheltered from extracellular immune system factors such as the complement system and antibodies. LLO also brings about dephosphorylation of histone H3 and deacetylation of histone H4 in the early phases of infection, before entry of L. monocytogenes into the host cell. The pore-forming activity is not implicated in causing the histone modifications. The modifications of the histones affect the down regulation of genes encoding proteins involved in the inflammatory response. Therefore, LLO may be significant in subverting the host immune response to L. monocytogenes. At its NH2-terminus it possesses a 25 residues long typical signal sequence excited during the secretion process. Moreover, in its NH2-terminus there is also a 19 amino acids PEST- like sequence that may target this toxin for degradation. The PEST-like sequence found in LLO and is considered crucial for virulence, given that mutants lacking the sequence lysed the host cell. Nevertheless, contrary to PEST's supposed role in protein degradation, evidence implies that the PEST-like sequence may control LLO production in the cytosol rather than increase degradation of LLO.

GOT2 is a pyridoxal phosphate-dependent enzyme which is found in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2. GOT2 participates in amino acid metabolism and the urea and tricarboxylic acid cycles. Both enzymes are homodimeric and demonstrate close homology.

DCXR catalyzes the NADPH-dependent reduction of numerous pentoses, tetroses, trioses, alpha-dicarbonyl molecules and L-xylulose. DCXR takes part in the uronate cycle of glucose metabolism. DCXR participates in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thus preventing osmolytic stress from occurring in the renal tubules.

Thiosulfate sulfurtransferase like domain containing 1 (TSTD1) is a member of a family of transferases, specifically the sulfurtransferases, which transfer sulfur-containing groups. TSTD1 is localized around the nuclear membranes. TSTD1 is expressed in a number of human tissues, including the kidney, liver, skeletal muscle, heart, colon, thymus, spleen, placenta and lung. TSTD1 may participate in cyanide detoxification, the formation of iron-sulfur proteins, and the modification of sulfur-containing enzymes.

Fibroblast Growth Factor-19 (FGF-19) is a member of the FGF family. FGF-19 interacts with FGFR1, FGFR2, FGFR3 and FGFR4. T FGF-19 takes part in the suppression of bile acid biosynthesis through downregulation of CYP7A1 expression, following positive regulation of the JNK and EPK1/2 cascades. FGF-19 stimulates glucose uptake in adiposytes and is a high affinity, heparin dependent ligand for FGFR4.

GIMAP6 is a member of the GTPases of immunity-associated proteins (GIMAP) family. GIMAP proteins contain GTP-binding and coiled-coil motifs, and may play roles in the regulation of cell survival. Decreased expression of this gene may play a role in non-small cell lung cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is found in a cluster with seven additional GIMAP genes on the long arm of chromosome 7.

ASPH hydroxylates an Asp or Asn residue in EGF domains. ASPH is involved in calcium homeostasis. ASPH is expressed from two promoters and goes through extensive alternative splicing. The encoded set of ASPH proteins share varying quantities of overlap near their N-termini although have considerable differences in their C-terminal domains resulting in distinct functional properties. The longest isoforms (a and f) include a C-terminal Aspartyl/Asparaginyl beta-hydroxylase domain that hydroxylates aspartic acid or asparagine residues in the EGF domain, including protein C, coagulation factors VII, IX, and X, and the complement factors C1R and C1S. Further isoforms diverge mainly in the C-terminal sequence and lack the hydroxylase domain, and some have been localized to the endoplasmic and sarcoplasmic reticulum.

Thiosulfate Sulfurtransferase Like Domain Containing 3, also known as TSTD3 contains 1 rhodanese domain which is characterized by an active site cysteine residue that has the ability to bind sulfane sulfur and catalyse sulfur transfer.

COMT catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to catechol substrates such as the neurotransmitters. This O-methylation results in one of the main degradative pathways of the catecholamine transmitters. COMT COMT is located in the postsynaptic neuron and is involved in the metabolism of catechol estrogen drugs used in the treatment of hypertension, asthma, Parkinson disease and the inactivation of catecholamine neurotransmitters though enzymatic degradation. COMT appears in tissues in 2 forms, a soluble form and a membrane-bound form which differ in their N-termini. COMT inhibitors increase its availability and are used in the treatment of patients with Parkinson's disease.

NFNB demonstrates the capability to reduce quinines. NFNB enzyme activates prodrugs in antibody directed enzyme prodrug therapy. NFNB reduces nitrofurazone, quinones and anti-tumor agent CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). The reduction of CB1954 results in the generation of cytotoxic species.

GDA is a member of the ATZ/TRZ family and is in charge for the hydrolytic deamination of guanine. GDA takes part in microtubule assembly. Multiple transcript variants encoding different isoforms have been found for GDA.

Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate as a cofactor which maintains the dTMP (thymidine-5-prime monophosphate) pool vital for DNA replication and repair. Thymidylate synthase plays an important role as a cancer chemotherapeutic agent. Thymidylate synthase is the primary site of action for 5-fluoro-2-prime-deoxyuridine and several folate analogs.

Branched Chain Amino-Acid Transaminase 2 (BCAT2) is a member of the class-IV pyridoxal-phosphate-dependent aminotransferase family. BCAT2 is a branched chain aminotransferase found in mitochondria. BCAT2 forms a dimer which catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. In addition, BCAT2 may actn as a transporter of branched chain alpha-keto acids.

Phosphoglycerate mutase 2 (PGAM2) is a member of the phosphoglycerate mutase family. PGAM is a dimeric enzyme which contains in separate tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). PGAM (Phosphoglycerate mutase) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. PGAM2 gene mutations cause muscle phosphoglycerate mutase efficiency, otherwise known as glycogen storage disease X.

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis.

OGG1 is a DNA glycosylase enzyme which takes part in base excision repair. OGG1 protein is the main enzyme accountable for the excision of 7,8-dihydro-8-oxoguanine (8-oxoG), a mutagenic base byproduct which arises as a result of exposure to reactive oxygen species (ROS). OGG1 shows beta lyase activity that nicks DNA 3 to the lesion.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a part of the 1-acyl-sn-glycerol-3-phosphate acyltransferase family. LPCAT1 is a key enzyme for remodeling phospholipids, including phosphatidylcholine. LPCAT1 possesses both acyltransferase and acetyltransferase activities and also mediates the conversion of 1-acyl-sn-glycero-3-phosphocholine (LPC) into phosphatidylcholine (PC). LPCAT1 presents a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively. LPCAT1 synthesizes phosphatidylcholine in pulmonary surfactant and therefore playing an important role in respiratory physiology.

E.Coli Acetate Kinase, also knowns as ACKA, catalyzes the formation of acetyl phosphate from acetate and ATP and also catalyzes the reverse reaction. ACKA takes part in synthesis of various ATP formed catabolically during anaerobic growth of the organism.

CysH (Phosphoadenosine phosphosulfate reductase) is a member of the PAPS reductase family, specifically those acting on a sulfur group of donors with a disulfide as acceptor. The 3 substrates of the CysH enzyme are adenosine 3',5'-bisphosphate, sulfite, and thioredoxin disulfide, whereas its two products are 3'-phosphoadenylyl sulfate and thioredoxin.

AKR1B1 is part of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. AKR1B1 catalyzes the reduction several aldehydes, including the aldehyde form of glucose, and thus involved in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. AKR1B1 catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Transgenic mice over expressing human aldose reductase show that AKR1B1 is a key player in ischemic injury and impairment of functional and metabolic recovery after ischemia. Aldose Reductase is an obligatory mediator of TNF-alpha signaling leading to an increase in the expression of adhesion molecules and increased binding of monocytes to the endothelium. AKR1B1 is a critical regulator of TNF-alpha-induced apoptotic signaling in endothelial cells.

Human Phosphoserine phosphatase (hPSP) is an important enzyme in the phosphorylated pathway of serine biosynthesis, which contributes a major portion of the endogenous L-serine. Similar to known L-3-phosphoserine phosphatases, it catalyzed the Mg2+-dependent hydrolysis of L-phosphoserine and an exchange reaction between L-serine and L-phosphoserine. Recently, its complex structures reveal that the open-closed environmental change of the active site, generated -helical bundle domain, is important to substrate by local rearrangement of the recognition and hydrolysis.

Glycolate oxidase (HAO1) belongs to the superfamily of the alpha hydroxy acid oxidases (HAO) enzymes. HAO1 catalyzes the FMN mediated oxidation of glycolate to glyoxylate and glyoxylate to oxalate with reduction of oxygen to hydrogen peroxide. HAO1 is most abundantly expressed in the liver and pancreas and is most active on twocarbon substrates such as glycolate. Lately, HAO1 has been identified as a key contributor to hyperoxaluria, a disorder in which large deposits of calcium oxalate form kidney stones.

Coproporphyrinogen Oxidase (CPOX) which is localized to the internal membrane space of erythrocytes takes part in the 6th phase of heme biosynthesis. CPOX catalyzes the oxidative decarboxylation of propionic acid side chains of rings A and B of coproporphyrinogen III. Mutations in human CPOX gene forecast the clinical result of the disease, with either hepatic hereditary coproporphyria or hematological manifestations of erythropoietic harderoporphyria.