Conformational proteins

MJ Sippl, S Weitckus. Detection of native-like models for ammo acid sequences of unknown thi ee-dimensional stiaicture in a data base of known protein conformations. Proteins 13 258-271, 1992. 

RM Fine, H Wang, PS Shenkm, DL Yarmush, C Levmthal. Predicting antibody hypervariable loop conformations. II Minimization and molecular dynamics studies of MCP603 from many randomly generated loop conformations. Proteins 1 342-362, 1986. 

AE Garcia, JG Harman. Simulations of CRP (cAMP)2 in noncrystalhne environments show a subunit transition from the open to the closed conformation. Protein Sci 5 62-71, 1996. 

Proteins fold on a time scale from p seconds to seconds. Starting from a random coil conformation, proteins can find their stable fold quickly, although the number of possible conformations is astronomically high. 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

Traditional methods for fabricating nano-scaled arrays are usually based on lithographic techniques. Alternative new approaches rely on the use of self-organizing templates. Due to their intrinsic ability to adopt complex and flexible conformations, proteins have been used to control the size and shape, and also to form ordered two-dimensional arrays of nanopartides. The following examples focus on the use of helical protein templates, such as gelatin and collagen, and protein cages such as ferritin-based molecules. 

Horwich, A. L., and Weissman, J. S. (1997). Deadly conformations—protein misfolding in prion disease. Cell 89, 499-510. 

Kettleborough, C.A., Saldanha, J., Heath, V.J., et al. (1991). Humanization of a mouse monoclonal-antibody by CDR-grafting—The importance of framework residues on loop conformation. Protein Eng., 4, 773-783. 

Corbeil, C. R., Moitessier, N. (2009) Docking ligands into flexible and solvated macromolecules. 3. Impact of input ligand conformation, protein flexibility, and water molecules on the accuracy of docking programs. J Chem Inf Model 49, 997-1009. 

Fat absorption of protein additives has been studied less extensively than water absorption and consequently the available data are meager. Although the mechanism of fat absorption has not been explained, fat absorption is attributed mainly to the physical entrapment of oil (7). Factors affecting the protein-lipid interaction include protein conformation, protein-protein interactions, and the spatial arrangement of the lipid phase resulting from the lipid-lipid interaction. Non-covalent bonds, such as hydrophobic, electrostatic, and hydrogen, are the forces involved in protein-lipid interactions no single molecular force can be attributed to protein-lipid interactions ( ). 

Horwich, A.L. Weissman, J.S. (1997). Deadly conformations—Protein misfolding in Prion Disease. Cell 89,499-510. 

Fig. 5.7 Periodically curved membrane conformations. Proteins filling the "holes" towards the corresponding three-dimei sional phase are indicated by filled units, whereas open units are free to diffuse along the bilayers. Successive changes towards asymmetric and constant (nonzero) mean curvature are shown from top to bottom.

Proteins contain many single bonds capable of free rotation. Theoretically, therefore, proteins can assume an infinite number of possible conformations but under normal biological conditions, they assume only one or a very small number of most stable conformations. Proteins depend upon these stable conformations for their specific biological functions. A functional protein is said to be in its native form, usually the most stable one. The three-dimensional conformation of a polypeptide chain is ultimately determined by its amino acid sequence (primary structure). Changes in that sequence, as they arise from mutations in DNA, may yield conformationally altered (and often less stable, less active, or inactive) proteins. Since the biological function of a protein depends on a... 

Structure of 3,3, 5,5 -tetraiodo-L-thyronine (T4). T4 is a substituted tyrosine or a diphenylether derivative of alanine. Positions in the outer phenolic ring have prime designations, in contrast to those in the inner ring. T4 is iodinated at positions 3 and 5 in both rings. [Modified and reproduced with permission from V. Cody, Thyroid hormone interactions molecular conformation, protein binding, and hormone action. Endocr. Rev. 1,140 (1980). (c)1980by the Endocrine Society.]... 

Petrella, R.J. and Karplus, M. (2004) The role of carbon-donor hydrogen bonds in stabilizing tryptophan conformations. Proteins Struct. Func. Genetics 54, 716-726. 

Y. Matsuo, K. Nishikawa. Assessment of a protein fold recognition method that takes into account four physicochemical properties Sidechain packing, solvation, hydrogen-bonding, and local conformation. Proteins. 1995, 23, 370-375. 

S. Sudarsanam, S. Srinivasan. Sequence-dependent conformational sampling using a database of phi(i)+l and psi(i) angles for predicting polypeptide backbone conformations. Protein Eng. 1997, 10, 1155-1162. 

A. Tramontano and A. M. Lesk. Common features of the conformations of antigen binding loops in immunoglobulins and application to modeling loop conformations. Proteins 73 231-245 (1992). 

One of the most important aspects of protein synthesis is the folding of polypeptides into their biologically active conformations. Despite decades of investigation into the physical and chemical properties of polypeptide chains, the mechanism by which a primary sequence dictates the molecule s final conformation is unresolved. It has become increasingly clear that many proteins require molecular chaperones to fold into their final three-dimensional conformations. Protein mis-folding is now known to be an important feature of several human diseases, including Alzheimer s disease and Creutzfeld-Jacob disease. 

Horwich AL, Weissman JS. Deadly conformations-protein misfolding in prion diseases. Cell 1997 89 499-510. 

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