Ribonuclease structure and

Christian B. Anfinsen, Sanford Moore, and William H. Stein Chemistry Ribonuclease, structure and activity... 

D Alessio, G., and Riordan, J. F., eds. (1997) Ribonuclease Structure and Functions, Academic Press, San Diego, California... 

M. Irie inG. D Alessio, J.F. Riordan, eds.. Ribonucleases Structures and Functions, Academic Press, USA, 1997. 

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. 

S. Moore and W. H. Stein (Rockefeller, New York) contributions to the understanding of the connection between chemical structure and catalytic activity of the active centre of the ribonuclease molecule. 

In addition to popular mesoporous silica materials, mesoporous silica supports with various morphologies have also been used for protein immobilization. Tang and coworkers synthesized lotus-leaf-like silica flakes with a three-dimensionally connected nanoporous structure and controllable thickness, which were used for immobilization of ribonuclease A [126]. The synthesized silica flakes have a thickness of200 nm, and a diameter of 3 mm, showing a much higher initial adsorbing rate of... 

Rait VK, O Leary TJ, Mason JT. Modeling formalin fixatin and antigen retrieval with bovine pancreatic ribonuclease A I—structural and functional alterations. Lab. Invest. 2004 84 292-299. 

Vanadium is beneficial and possibly essential for humans. It is certainly essential for a number of organisms. Vanadate (oxidation state V) and its derivatives are phosphate analogues, showing both ground state and transition state analogy (both structural and electronic) with phosphorus compounds. The analogy of five-coordinate vanadium compounds with the transition state of phosphate ester hydrolysis is well documented, and explains why so many vanadium compounds are potent inhibitors of phosphatases, ribonucleases and ATPases. 

The fact that a denatured protein can spontaneously return to its native conformation was demonstrated for the first time with ribonuclease, a digestive enzyme (see p. 266) consisting of 124 amino acids. In the native form (top right), there are extensive pleated sheet structures and three a helices. The eight cysteine residues of the protein are forming four disulfide bonds. Residues His-12, Lys-41 and His-119 (pink) are particularly important for catalysis. Together with additional amino acids, they form the enzyme s active center. 

A relative of the kinases is adenylate cyclase, whose role in forming the allosteric effector 3, 5 -cyclic AMP (cAMP) was considered in Chapter 11. This enzyme catalyzes a displacement on Pa of ATP by the 3 -hydroxyl group of its ribose ring (see Eq. 11-8, step a). The structure of the active site is known.905 Studies with ATPaS suggest an in-line mechanism resembling that of ribonuclease (step a, Eq. 12-25). However, it is Mg2+ dependent, does not utilize the two-histidine mechanism of ribonuclease A, and involves an aspartate carboxylate as catalytic base.906 All isoforms of adenylate cyclase are activated by the a subunits of some G proteins (Chapter 11). The structures907 of Gsa and of its complex with adenylate kinase905 have been determined. The Gsa activator appears to serve as an allosteric effector. 

With large molecules X-ray crystallographic structure determination may be desirable prior to synthetic activities. Incredibly, ribonuclease, insulin, and a number of smaller peptides have been synthesized. 

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