P Proteins

OC/P-Proteins. The most frequent domain stmctures observed in proteins are those having a mixture of hehces and sheets. One of the largest... 

EB Shemerman, CL Brooks III. Molecular picture of folding of a small a/p protein. Proc Natl Acad Sci USA 95 1562-1567, 1998. 

Richardson, J.S. The anatomy and taxonomy of protein stmcture. Adv. Prot. Chem. 34 167-339, 1981. Rossmann, M.G., Argos, P. Protein folding. Annu. Rev. 

We have described a general relationship between structure and function for the a/p-barrel structures. They all have the active site at the same position with respect to their common structure in spite of having different functions as well as different amino acid sequences. We can now ask if similar relationships also occur for the open a/p-sheet structures in spite of their much greater variation in structure. Can the position of the active sites be predicted from the structures of many open-sheet a/p proteins ... 

In this structure the loop regions adjacent to the switch point do not provide a binding crevice for the substrate but instead accommodate the active-site zinc atom. The essential point here is that this zinc atom and the active site are in the predicted position outside the switch point for the four central parallel p strands, even though these p strands are only a small part of the total structure. This sort of arrangement, in which an active site formed from parallel p strands is flanked by antiparallel p strands, has been found in a number of other a/p proteins with mixed p sheets. 

Janin, J., Chothia, C. Packing of a-helices onto p-pleat-ed sheets and the anatomy of a/p-proteins. /. Mol. Biol. 143 95-128, 1980. 

The active site of subtilisin is outside the carboxy ends of the central p strands analogous to the position of the binding sites in other a/p proteins as discussed in Chapter 4. Details of this active site are surprisingly similar to those of chymotrypsin, in spite of the completely different folds of the two enzymes (Figures 11.14 and 11.9). A catalytic triad is present that comprises residues Asp 32, His 64 and the reactive Ser 221. The negatively charged oxygen atom of the tetrahedral transition state binds in an oxyanion hole,... 

Thornton, J.M., Gardner, S.P. Protein motifs and data-base searching. Trends Biochem. Sci. 14 300-304, 1989. 

Eisenberg, D., Hill, C.P. Protein crystallography more surprises ahead. Trends Biochem. Sci. 14 260-264, 1989. 

Mrochek, J. E., Dinsmore, S. R., Tormey, D. C., and Waalkes, T. P., Protein-bound carbohydrates in breast cancer, liquid-chromatographic analysis for mannose, galactose, fucose, and sialic acid in serum, Clin. Chem., 22, 1516, 1976. 

Figure 31 Scheme for the protein-binding, diffusional, and partitioning processes and barriers that are encountered by a highly lipophilic and membrane-interactive drug (D) as it permeates through a cell within a continuous monolayer, h and h, thicknesses of the aqueous boundary layers. kd and ka, dissociation and association binding constants, respectively. P, protein molecule. Permeability coefficients Effective, Pe aqueous boundary layer, PABL and PW apical membrane, Pap basolateral membrane, Pbl. 

Myelin basic protein. In PNS myelin, MBP varies from approximately 5% to 18% of total protein, in contrast to the CNS, where it is close to 30% [ 1 ]. In rodents, the same four 21,18.5,17 and 14kDa MBPs found in the CNS are present in the PNS. In adult rodents, the 14kDa MBP is the most prominent component and is termed Pr in the PNS nomenclature. The 18.5 kDa component is present and is often referred to as the P, protein in the nomenclature of peripheral myelin proteins. Another species-specific variation in human PNS is that the major basic protein is not the 18.5 kDa isoform that is most prominent in the CNS but rather a form of about 17 kDa. It appears that MBP does not play as critical a role in myelin structure in the PNS as it does in the CNS. For example, the shiverer mutant mouse, which expresses no MBP (Table 4-2), has a greatly reduced amount of CNS myelin, with no compaction of the major dense line. By contrast, shiverer PNS has essentially normal myelin,both in amount and structure, despite the absence of MBP. This CNS/PNS difference in the role of MBP is probably because the cytoplasmic domain of P0 has an important role in stabilizing the major dense line of PNS myelin. Animals doubly deficient for P0 and MBP have a more severe defect in compaction of the PNS major dense line than P0-null mice, which indicates that both proteins contribute to compaction of the cytoplasmic surfaces in PNS myelin [23],... 

Nestler, E. J. and Greengard, P. Protein Phosphorylation in the Nervous System. New York Wiley, 1984. 

Figure 6. The effect of different ration levels of calcium (Ca = 0.3% and Ca2 = 1.2%) and phosphorus (P1 = 0.3% and P2 = 1.2%) on fecal calcium and phosphorus in mice fed soy (S) or egg white (E) diets. Top Main effect, ca. P < 0.0001. Bottom P-protein interaction P < 0.0001.

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