Enzymes mono-zinc

The first zinc enzyme to be discovered was carbonic anhydrase in 1940, followed by car-boxypeptidase A some 14 years later. They both represent the archetype of mono-zinc enzymes, with a central catalytically active Zn2+ atom bound to three protein ligands, and the fourth site occupied by a water molecule. Yet, despite the overall similarity of catalytic zinc sites with regard to their common tetrahedral [(XYZ)Zn2+-OH2] structure, these mononuclear zinc enzymes catalyse a wide variety of reactions, as pointed out above. The mechanism of action of the majority of zinc enzymes centres around the zinc-bound water molecule,... 

ALAD (also known as porphobilinogen synthase) is a cytoplasmic enzyme that catalyzes the formation of the mono-pyrrole porphobilinogen (PEG) from two molecules of ALA with elimination of two molecules of water. The enzyme requires zinc ions as a cofactor and reduced sulfhydryl groups at the active site and is therefore susceptible to inhibition by lead. 

Fig. 9.2 Mechanism for the hydrolysis of biapenem catalyzed by a mono-zinc lactamase CphA from A. hydrophila. Two mechanisms have been included, and the green arrows mean a viable pathway, while the red arrows represent a non-productive pathway [38], Reprinted with permission from (Wu S, Xu D, Guo H (2010) QM/MM studies of monozinc /i-lactamase CphA suggest that the crystal structure of an enzyme—intermediate complex represents a minor pathway, J Am Chem Soc 132 17986-17988). Copyright (2010) American Chemical Society...

There has been particular recent interest in zinc nitrate complexes as coordination models for bicarbonate binding in carbonic anhydrase. The mono- or bidentate coordination modes have been studied with tris-pyrazolyl borate complexes and can be rationalized in the context of the enzyme activity.433 Caution in this comparison is introduced by ab initio calculations on these model systems demonstrating both monodentate and bidentate coordination energy minima for nitrate binding to zinc 434... 

As mentioned earlier, by far the largest number of zinc enzymes are involved in hydrolytic reactions, frequently associated with peptide bond cleavage. Carboxypeptidases and ther-molysins are, respectively, exopeptidases, which remove amino acids from the carboxyl terminus of proteins, and endopeptidases, which cleave peptide bonds in the interior of a polypeptide chain. However, they both have almost identical active sites (Figure 12.4) with two His and one Glu ligands to the Zn2+. It appears that the Glu residue can be bound in a mono- or bi-dentate manner. The two classes of enzymes are expected to follow similar reaction mechanisms. 

In many cases nucleic acid polymerases are zinc-dependent enzymes. Hutchinson et al.45 have drawn upon the use of phosphonoacetic acid and phosphonoformic acid and introduced mono- and bis-thiopyrophosphate. They propose that the inhibition of influenza virus occurs by inhibition of RNA transcriptase45. By using 31P-NMR they... 

Eiichi Kimura is retired from the Department of Medicinal Chemistry at Hiroshima University in Japan. His recent research interests have included the supramolecular chemistry of macrocyclic polyamines and their use in molecular recognition and as zinc-enzyme models. These interests have led to the development of fluorophore sensors for Zn(II) [8] use of macrocycles to effect selective recognition of anions [9], nucleobases in polynucleotides [10], thymidine mono- and diphosphate nucleotides (11), carbonic anhydrase and carboxypeptidase [12], and development of Zn(II)-macrocycle anti-HIV agents [13], In May 2004, he received a Purple Ribbon Award from the Emperor of Japan. 

Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 1 Sites Copper Proteins with Type 2 Sites Cytochrome Oxidase Iron Heme Proteins Dioxygen Transport Storage Iron Heme Proteins Electron Transport Iron Heme Proteins, Mono- Dioxygenases Iron Heme Proteins, Peroxidases, Catalases Catalase-peroxidases Iron Proteins with Dinuclear Active Sites Iron Proteins with Mononuclear Active Sites Iron-Sulfur Proteins Peptide Metal Interactions Zinc DNA-binding Proteins Zinc Enzymes. 

Several porphyrins bind OPH with nniqne spectrophotometric characteristics resnlting however, in order to form a porphyrin-enzyme complex that is sensitive to the presence of snbstrates of the enzyme, a copper-complexed porphyrin is necessary [30]. Two candidates, a copper-complexed TPPSi and copper-complexed TPPCi (mono(4-carboxy phenyl) porphyrin Rj = CO2A R2 = 803 ) inhibit the activity of OPH in a mixed manner. Mixed inhibition is the inhibition of enzyme activity in a manner such that the maximal enzymatic rate and the concentration needed to achieve half of that rate are both changed. The intersection of the cnrves in the absence and presence of the inhibitor occnrs in the second qnadrant of the Lineweaver-Bnrk plot. Mixed type inhibition involves the interaction of the inhibitor at two or more locations on the enzyme with one of these being the active site. The spectrophotometric characteristics of the porphyrin-enzyme complex are different depending on whether the apo or wild-type enzyme is bonnd by the copper-complexed porphyrins however, the spectrophotometric characteristics are identical for the interaction of TPPSi or TPPCi with either version of the enzyme. Other porphyrins snch as zinc-and iron-complexed TPPSi as well as the metal-free TPPSi and TPPCi do not inhibit the enzymatic activity of OPH. 

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