Deoxyribonuclease structure

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

Chen B, Costantino HR, Liu J, Hsu CC, Shire SJ. Influence of calcium ions on the structure and stability of recombinant human deoxyribonuclease I in the aqueous and lyophilized states. J Pharm Sci 1999 88(4) 477 182. 

All of the bacterial deoxyribonucleases that have been examined in detail possess a specificity directed in varying degrees toward the secondary structure of the polydeoxynucleotide. With one recent exception, none of the deoxyribonucleases shows a simple base specificity whereby they attack phosphodiester bonds adjacent to a single base. However, it is now clear that several of the endonucleases may possess an extremely high order of specificity and have the capacity to recognize and attack one or a few phosphodiester bonds in polydeoxynucleotide chains composed of many thousands of internucleotide linkages. 

In this charter, wc will focus on the present insights into the structure-activity relationship and the clinical situation of this enzyme without attempting to iiuaiuic U relevant studies. For reviews on the biochemistry up to l9W, largely refer to the work of M. Laskowsfci [1], who was closely Involved in early studies on DNase I, and of S. Moore [9]. Moore shared with W. Stein Nobel Prize in Chemistry in 1972 fra their work on the chemical structures of pancreatic ribanudesae and deoxyribonuclease [ID]. 

Sk Moore and W. H. Stain. Chemical structure of pancreatic ribonudease and deoxyribonuclease- Science 160 458-464 (1673). 

Ribonuclease from other mammalian sources may have several carbohydrate fragments in their structures. Thus, ribonuclease B from porcine pancreas contains at least three carbohydrate moieties, and these are attached9 at asparagine residues 21, 34, and 76. The carbohydrate moieties present at residues 21 and 76 are considerably more complex than that at residue 34, and their structures are under investigation in several laboratories. The carbohydrate portions of the isoenzymes of deoxyribonuclease are similar in structure to those from the ribonucleases.11 As ribonuclease and deoxyribonuclease originate in the same organ, it is possible that the same pathways and enzymes are utilized for the biosynthesis of the carbohydrate moieties of both enzymes. 

S. Moore and W.H. Stein. 1973. Chemical structures of pancreatic rihonuclease and deoxyribonuclease Science 180 458-464. (PubMed)... 

T.-H. Liao, J. Salnikow, S. Moore, and W. H. Stein. Bovine pancreatic deoxyribonuclease A isolation of cyanogen bromide peptides complete covalent structure of the polypeptide chain. J. Biol. Chem. 248 1489-1495 (1973). [Published erratum appeared in J. Biol. Chem. 267 1951 (1992).]... 

T. L. Poulos and P. A. Price. Some effects of calcium ions on the structure of bovine pancreatic deoxyribonuclease A. J. BioL Chem. 247 2900-2904 (1972). 

At the level of primary structure, several recent experiments have shown the effect of base sequence on the local structure of DNA. A dramatic example is the crystal structure of d(CpG) as determined by Rich and coworkers ( ). This molecule crystallizes in a left-handed double helical form called Z-DNA, which is radically different in its structural properties from the familiar right-handed B-DNA structure. Dickerson and Drew (10) showed in the crystal structure of the dodecanucleotide d(CGCGAATTCGCG) that the local twist angle of a DNA double helix varies with sequence. Deoxyribonuclease I cuts the phosphodiester backbone of the dodecanucleotide preferentially at sites of high twist angle (l 1). From these and other (12,13) experiments we see that the structure of DNA varies with base sequence, and that enzymes are sensitive to these details of structure. 

Because of its tendency to polymerize, G-actin has been difficult to crystallize. However, it forms crystalline complexes with several other proteins, e.g., deoxyribonuclease 1, a fragment of gelsolin, and profilin, which block polymerizafion and if has recently been crystallized as the free ADP complex. The fhree-dimensional structure of the actin is nearly the same in all cases. The molecule folds into four domains, the ATP binding site being buried in a deep cleft. The atomic structure (Fig. 7-10) resembles that of hexo-kinase, of glycerol kinase, and of an ATP-binding domain of a chaperonin of fhe Hsp 70 family. As with the kinases, actin can exist in a closed and more open conformations, one of which is seen in the profilin complex. Addition of 1 mM Mg + or 0.1 M KCl to a solution of G-actin leads to spontaneous transformation into filaments of F-actin (Figs. 7-10 and... 

The role of the divalent metal ions present in natural phosphodiesterases became clear in bovine pancreatic deoxyribonuclease I (DNase I), the first endonuclease structure determined by X-ray crystallography. The nucleophilic attack of a water molecule activated by a histidine residue is facilitated by the interaction of a calcium ion with the phosphate group to be cleaved (291). Glutamic and aspartic residues involved in magnesium binding have been identified in the crystal structure of four type II restriction enzymes EcoRl (292), EcoRV (293), Pvull (294), and BamHl (295), as well as in that of the repair... 

Bernardi G. (1965a). Dimeric structure and allosteric properties of spleen acid deoxyribonuclease J. Mol. Biol. 13 603-605. 

There are several lines of experimental evidence to support the Watson-Crick structure (Mahler and Cordes, 1966). We are concerned here only with the type of evidence obtainable from infrared spectroscopy, an example of which is the following Thin sheets of sodium or lithium DNA, equilibrated with D2O, show charactmstic bands at 1685, 1665, and 1644 cm (weak bands at 1620 and 1575 cm ) that have been assigned to C=0, C=N, and C=C stretching and NHj deformation vibrations of the bases in the helical pattern. The band intensity at 1685 cm of DNA in DjO is reduced significantly, while those at 1665 and 1620 cm are increased when the molecular structure is denatured by heat, alkali, formamide, or deoxyribonuclease [see below] (Bradbury et al., 1961 Kyogoku et al, 1961). 

Hewish, D. R., and Burgoyne, L. A. (1973). Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochem. Biophys. Res. Commun. 52,. StM-SlO. 

Nickel, Ni a metai present only in traces in living systems. In particular, it seems to be associated with RNA. A nickei metalloprotein, named nickeloplas-min has been isolated from human and rabbit serum, but its function is not known. Ni protects the structure of the ribosome against heat denaturation, and it restores the sedimentation characteristics of E. coli ribosomes that have been denatured by EDTA. Ni can activate some enzymes in vitro, e.g. deoxyribonuclease, acetyl CoA synthetase and phosphoglucomu-tase. Ni deficiency causes changes in the ultrastructure of the liver and alters the level of cholesterol in the liver membranes. It may be important in the regulation of prolactin. 

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