Ribonuclease domain structure

Leucine residues 2, 5, 7, 12, 20, and 24 of the motif are invariant in both type A and type B repeats of the ribonuclease inhibitor. An examination of more than 500 tandem repeats from 68 different proteins has shown that residues 20 and 24 can be other hydrophobic residues, whereas the remaining four leucine residues are present in all repeats. On the basis of the crystal structure of the ribonuclease inhibitor and the important structural role of these leucine residues, it has been possible to construct plausible structural models of several other proteins with leucine-rich motifs, such as the extracellular domains of the thyrotropin and gonadotropin receptors. 

Sambashivan, S., Liu, Y., Sawaya, M. R., Gingery, M., and Eisenberg, D. (2005). Amyloidlike fibrils of ribonuclease A with three-dimensional domain-swapped and nativelike structure. Nature 437, 266-269. 

Parallel /3 structure usually forms large, moderately twisted sheets such as in Fig. 23, although occasionally it rolls up into a cylinder with helices around the outside (e.g., triosephosphate isomerase). Large antiparallel sheets, on the other hand, usually roll up either partially (as in the first domain of thermolysin or in ribonuclease) or completely around to join edges into a cylinder or barrel. Occurrence, topology, and classification of /3 barrels will be discussed in Section III,D, but here we will consider the interaction between the /3 sheets on opposite sides of the barrel, especially in terms of the angle at which opposite strands cross. 

Ribonuclease H is a small, single domain protein that eleaves RNA from RNA-DNA hybrids. RNase H from E. coli T = 66 °C) has been structurally studied by NMR spectroscopy.Hydrogen exchange NMR experiments have been used to examine the structural distribution of stability in RNase H from T. thermophiliis = 86 °C) and to compare its stability with that of the homologous RNase H from the mesophilic E. The general distribution... 

Davies JF, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 1991 252 88-95. 

Chattopadhyay D, Finzel BC, Munson SH, Evans B, Sharma SK, Strakalattis NA, et al. Crystallographic analysis of an active HIV-1 ribonuclease H domain show structural features that distinguish it from the inactive form. Acta Crystallogr 1993 D49 423-427. 

During last decades the domains C-2 symmetry (the dyad rotation symmetry) of low-B palindrome was established in many enzymes (chymotrypsin, trypsin, aspartyl proteinases, HIV-1 protease, carboxypeptidase A, phospholipase A-2 ribonuclease, etc.) (Lumry, 2002 and references therein). It is proposed that the pair domain closure causes constrain of pretransition state complex that activates cleavage or formation of chemical bonds. Thus control of strong bonds by the cooperation of many matrix or knots bonds takes place. As an example, in the active site of carboxypeptidase A the zinc ion is attached to one of the catalytic domains by histidine 69 and glutamine 72 and connected by hystidine 196 to the second domain. Similar structures were found in the chymotrypsin and pepsin active sites where protons are driven under compression of the domains closure. 

Manganese(II) ions may also be employed in the hydrolases that compose the ribonuclease H domain of reverse transcriptases (3, 4). Many of these enzymes, which may employ either Mn" or Mg11, are found in a variety of organisms where they may or may not be essential (e.g., Escherichia coli) (3, 4). This class of enzymes catalyzes the hydrolysis of DNA-RNA hybrids. However, retroviral reverse transcriptases are critical for the replication of retroviruses, and Mn11 may be the required cofactor for these ribonuclease hydrolases to function (3, 4). One example of this family of hydrolase enzymes is the RNase H enzyme from HIV-I. This enzyme has been crystallographically characterized (11). In the crystal structure at 2.4-A resolution, the two Mn 1 ions are separated by a distance of about 4 A. They are bound to carboxylate residues that are located near the surface of the enzyme. One of these carboxylates bridges the two manganese... 

The tertiary structure describes the complete three-dimensional stmcture of the whole polypeptide chain. It includes the relationship of different domains formed by the protein s secondary structure and the interactions of the amino acid substituent -R groups. An example of a protein chain with a-helices and /3-folding, the enzyme ribonuclease, is shown in Fig. 1.17. The specific folding of a protein is only thermodynamically stable within a restricted range of environmental parameters, i.e. the right temperature, pH and ionic strength. Outside of this range, the protein could unfold and lose its activity. 

FIGURE 15 Examples o a + proteins, (a) Ubiquitin, (b) Papain consists of one alpha-helix and four strands of antiparallel beta-sheet, (c) ribonuclease A, and (d) N-terminal domain of E. co//glutamine phosphoribosylpyrophosphate (Prpp) amidotransferase that contains a four structural layers appa. 

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