P-conformer

Figure 4 The energy landscape of the pnon protein (Pi P) (residues 124-226) in vacuum, obtained by principal coordinate analysis followed by the minimal energy envelope procedure. Two large basins are seen. One basin is associated with the native Pi P conformation the other is associated with partially unfolded conformations.

The catalytic cycle of the Na+/K+-ATPase can be described by juxtaposition of distinct reaction sequences that are associated with two different conformational states termed Ei and E2 [1]. In the first step, the Ei conformation is that the enzyme binds Na+ and ATP with very high affinity (KD values of 0.19-0.26 mM and 0.1-0.2 pM, respectively) (Fig. 1A, Step 1). After autophosphorylation by ATP at the aspartic acid within the sequence DKTGS/T the enzyme occludes the 3 Na+ ions (Ei-P(3Na+) Fig. la, Step 2) and releases them into the extracellular space after attaining the E2-P 3Na+ conformation characterized by low affinity for Na+ (Kq5 = 14 mM) (Fig. la, Step 3). The following E2-P conformation binds 2 K+ ions with high affinity (KD approx. 0.1 mM Fig. la, Step 4). The binding of K+ to the enzyme induces a spontaneous dephosphorylation of the E2-P conformation and leads to the occlusion of 2 K+ ions (E2(2K+) Fig. la, Step 5). Intracellular ATP increases the extent of the release of K+ from the E2(2K+) conformation (Fig. la, Step 6) and thereby also the return of the E2(2K+) conformation to the EiATPNa conformation. The affinity ofthe E2(2K+) conformation for ATP, with a K0.5 value of 0.45 mM, is very low. 

The Na+/K+-ATPase is the only enzyme known to interact with CTS, which reversibly bind to the extracellular side of the Na+/K+-ATPase at the E2-P conformational state [E2-P ouabain] and inhibit ATP hydrolysis and ion transport (Fig. lb, step 4). 

It has been established by substitution of for Mg that, prior to phosphorylation, the divalent cation binds at a cytosolic site with a stoichiometry of about 1 mol per phosphorylation site [124,125]. These experiments also demonstrated that the phosphorylation rate is sensitive to the nature of the divalent cation bound. With Mg bound, the phosphorylation rate is about 20 times faster than with Ca bound. The divalent cation dissociates after dephosphorylation, suggesting that it is tightly bound to the phosphoenzyme during the reaction cycle. It was also demonstrated that the type of divalent cation that occupies the divalent cation site required for phosphorylation is important for the step 2K E2-P to 2K E2 P to 2K E2 [124,125]. With Mg bound, the 2K E2-P conformer is -sensitive, whereas with Ca bound, the intermediate is -insensitive. 

CrATP, a suicide inhibitor of Ca -ATPase [178], that arrests the enzyme in a Ca occluded E[ P state, also produced E -type crystals very similar to those obtained with lanthanides [119]. These observations further support the assignment of the PI-type crystals to the Ei and E P conformation of the Ca -ATPase. 

X-ray diffraction analysis shows the protein to be a globular structure, consisting of four a-heli-cal stretches interrupted by bends and loops. It appears devoid of any P-conformation and contains a single stabilizing disulfide linkage involving cysteine numbers 58 and 105 (Figure 9.1). 

A greater understanding of the MM2 program is needed to implement the new -2 option for the dihedral driver. In MM2, a temporary file stores the coordinates at the end of each optimization for use as starting positions for the next optimization. The procedures that create these files had to be changed. An alternative to modification of MM2, used previously (3.), was to create separate input files for each ( ), P conformation of interest. This allowed use of the standard driver with a 0 increment size. Special programs could be used to prepare all of the input files. The check of... 

Cook et al. (86TL3853) found the conformational equilibrium of 5-Me-5-C6H4X(p)-l,3-dioxane to be strongly dependent on the electron-withdrawing character of the phenyl substituent more electronegative substituents shift the equilibrium to the 5-eq-MQ-5-ax-C( i X p) conformer A (Scheme 11). 

Faraldo-Gomez, J.D., Forrest, L.R., Baaden, M., Bond, P.J., Domene, C., Patargias, G., Cuthbertson, J., Sansom, M.S.P. Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations. Proteins Struct. Funct. Bioinformatics 2004, 57, 783-91. 

Ciani B, Hutchinson EG, Sessions RB, Woolfson DN. A designed system for assessing how sequence affects a to p conformational transitions in proteins. J Biol Chem 2002 277 10150-10155. 

The p Conformation Organizes Polypeptide Chains into Sheets... 

Interpretation of Infrared Spectra in Terms of Protein Conformation. With respect to ft structure the interpretation of infrared spectra of wet and dry membranes is straightforward. There is no evidence for P conformation in any of the systems examined. Since the / structure can be produced by denaturation there appear to be no constraints... 

We have seen that some polypeptides assume an extended P conformation while others form helices. 

P conformation of 60 knotted chains 74 torsion angles 60 Peptide deformylase 627 Peptide hormone(s). See also Chapter 30 amidationof 522 Peptide linkage 51,55s cis 56s... 

If peptide chains can be oriented in a regular fashion, it may be useful to measure infrared linear dichroism.24 25 Absorption spectra are recorded by passing plane polarized light through the protein in two mutually perpendicular directions, with the electric vector either parallel to the peptide chains or perpendicular to the chains. Such a pair of spectra is shown in Fig. 23-3A for oriented fibrils of insulin. In this instance, the insulin molecules are thought to assume a P conformation and to be stacked in such a way that they extend transverse to the fibril axis (a cross-P structure). When the electric vector is parallel to the fibril axis, it is perpendicular to the peptide chains. Since the amide I band is dominated by a carbonyl stretching motion that is perpendicular to the... 

Natta, G. and Corradini, P. Conformation of linear chains and their mode of packing in the crystal state. J. Polymer Sci. 39, 29 (1959) see also Natta, G., Corradini, P. and Porri, D. Rend. Accad. Nazi. Lincei 20, 728 (1956)... 

Ab initio methods also appear to be useful for predicting the M- to P-conformational transition barrier for reactive species, such as enolate 8. It is known that the presence of an (iS7-C3-substituent will favor the /17-con former in which the C-3 substituent adopts a pseudoequatorial arrangement. Consequently, deprotonation of C-3 at low temperature of certain benzodiazepines can result in single, conformationally chiral, nonracemic enolates locked in the /(/-configuration. The inversion barrier for enolate 8 at 195 K is calculated by DFT methods to be 17.5 kcal mol-1, which compares with 12.4 kcal mol-1 for the derivative where the N-l group is methyl instead of isopropyl <2003JA11482>. These results were used to explain the enantioselective C-3-alkylation method discussed in... 

Fraser,R.D.B MacRae,T.P. "Conformation in Fibrous Proteins", Academic Press, New York, 1973. 

In the case of tertiary amides, the planar arrangement of a-hydroxy-amide moieties is not favored due to bulky substituents. The repulsion between the N-alkyl substituents and the hydrogen atom attached to the distal Csp3 atom destabilizes the T structures of tertiary amides of (R,R [-tartaric acid [18,21,22]. As a result, the N,N,N ,N -tetramethyldiamide of (R,R [-tartaric acid is found in crystals in the G-p+p+ conformation, in which the main carbon chain is bent and the... 

Solvation effects, as calculated with the use of the AMSOL method, affect the confomational preferences of (i ,i )-tartaric acid amides, so that their lowest-energy structures are different from the G+aa conformers favored in isolated molecules. Hydratation favores the Tact conformation for the primary amides and the G-p+p+ conformation for the tertiary amides of (R,R (-tartaric acid. 

Reid, R. C. Kelso, M. J. Scanlon, M. J. Fairlie, D. P. Conformationally constrained macro-cycles that mimic tripeptide /1-strands in water and aprotic solvents. J. Am. Chem. Soc. 2002, 324, 5673-5683. 

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