Monomeric enzymes

Carboxypeptidases are zinc-containing enzymes that catalyze the hydrolysis of polypeptides at the C-terminal peptide bond. The bovine enzyme form A is a monomeric protein comprising 307 amino acid residues. The structure was determined in the laboratory of William Lipscomb, Harvard University, in 1970 and later refined to 1.5 A resolution. Biochemical and x-ray studies have shown that the zinc atom is essential for catalysis by binding to the carbonyl oxygen of the substrate. This binding weakens the C =0 bond by... 

It is a complex enzyme of molecular weight no greater than 40,000 in monomeric form. Chamical Abstracts Registry No. 9039-61-6... 

The tridentate ligands C, L and M are effective catalysts for the enantioselective addition of dialkylzincs to aromatic aldehydes16,17. In particular, ligands L and M qualify as members of the chemical enzyme (chemzyme) class of synthetic reagents17, since they function in a predictable, clear-cut mechanistic way. As demonstrated by X-ray diffraction, the actual catalyst is a monomeric zinc chelate 2 formed in toluene at 50 C by reaction of L or M with one equivalent of diethylzinc. 

I topoisomerase of mammals is a 100 kD monomeric protein whose activity is ATP-independent. This enzyme binds to double-stranded DNA and cleaves one of the DNA strands of the duplex, simultaneously forming an enzyme-DNA covalent bond between a tyrosine residue and the 3 -phosphate of the cleaved DNA. The type II topoisomerases are dimeric enzymes, which are ATP-dependant. Two isoforms of topoisomerase II exist, topoisomerase a and (3, with apparent molecular weights of 170 and 180 kD. Topoisomerase... 

Most of the enzymes are built of homo or heteromultimeric structures. For the sake of simplification, in the figures only the structures of the monomeric unit of the homomultimer will be shown. 

There are four different classes of nitrate reductases (234). The nitrate reductases from D. desulfuricans show a strong homology to the a-subunit of the class of periplasmic respiratory nitrate reductases, and also to some of the enzymes that are included on the class of cytoplasmic assimilatory nitrate reductases. Because of this fact, a proposal was made for a new class of monomeric NAP, which contains the minimal arrangement of metal centers to perform nitrate reduction one [4Fe-4S] cluster and a Mo bound to two MGD. 

Cosme J, Johnson EF. Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding. /FtoZ Chem 2000 275 2545-53. 

Xanthine oxidase (XO) is not only an important biological source of ROS but also the enzyme responsible for the formation of uric acid associated with gout leading to painful inflammation in the joints. The XO inhibition effect by the enzymatically synthesized poly(catechin) increased as an increasing concentration of catechin units, while the monomeric catechin showed almost negligible inhibition effect in the same concentration range. ° This markedly amplified XO inhibition activity of poly(catechin) was considered to be due to effective multivalent interaction between XO and the condensed catechin units in the poly (catechin). 

Further indications for an additional subunit were provided by a crosslinking analysis of C Eg solubilized H,K-ATPase, which exhibited ATPase and phosphatase activities, and ligand affinities comparable to the native enzyme [70]. Glutar-aldehyde treatment of soluble protein fractions resolved on a linear glycerol gradient revealed no active fraction enriched in monomeric (A/p = 94 kDa) H,K-ATPase. Instead, K -ATPase activity was only obtained in fractions enriched in particles of Mr = 175 kDa. This size also suggested that the functional H,K-ATPase unit is a heterodimer of a catalytic subunit and an additional subunit, since the apparent molecular mass of 175 kDa is probably too small to be a homodimer of the catalytic subunit. 

Component B is a monomeric reductase with a molecular weight of 35,000 and contains per mol of enzyme, 1 mol of FMN, 2.1 mol of Fe, and 1.7 mol of labile sulfur. After reduction with NADH, the ESR spectrum showed signals that were attributed to a [2Fe-2S] structure and a flavo-semiquinone radical (Schweizer et al. 1987). The molecular and kinetic properties of the enzyme are broadly similar to the Class IB reductases of benzoate 1,2-dioxygenase and 4-methoxybenzoate monooxygenase-O-demethylase. 

Gierer, J. Opara, A. E. Enzymic degradation of lignin. Action of peroxidase and laccase on monomeric and dimeric model compounds. Acta Chem. Scand. 1973, 27,... 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

The dihydrofolate reductase enzyme (DHFR) is involved in one-carbon metabolism and is required for the survival of prokaryotic and eukaryotic cells. The enzyme catalyzes the reduction of dihydrofolate to tetrahydrofolate, which is required for the biosynthesis of serine, methionine, purines, and thymidylate. The mouse dihydrofolate reductase (mDHFR) is a small (21 kD), monomeric enzyme that is highly homologous to the E. coli enzyme (29% identify) (Pelletier et al., 1998). The three-dimensional structure of DHFR indicates that it is comprised of three structural fragments F[l], F[2] andF[3] (Gegg etal., 1997). 

The importance of hydrophobic binding interactions in facilitating catalysis in enzyme reactions is well known. The impact of this phenomenon in the action of synthetic polymer catalysts for reactions such as described above is significant. A full investigation of a variety of monomeric and polymeric catalysts with nucleophilic sites is currently underway. They are being used to study the effect of polymer structure and morphology on catalytic activity in transacylation and other reactions. 

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