Stereochemical helical molecules

The phase problem and the problem of arbitration. Fibrous structures are usually made up of linear polymers with helical conformations. Direct or experimental solution of the X-ray phase problem is not usually possible. However, the extensive symmetry of helical molecules means that the molecular asymmetric unit is commonly a relatively small chemical unit such as one nucleotide. It is therefore not difficult to fabricate a preliminary model (which incidently provides an approximate solution to the phase problem) and then to refine this model to provide a "best" solution. This process, however, provides no assurance that the solution is unique. Other stereochemically plausible models may have to be considered. Fortunately, the linked-atom least-squares approach provides a very good framework for objective arbitration independent refinements of competing models can provide the best models of each kind the final values of n or its components (eqn. xxiv) provide measures of the acceptability of various models these measures of relative acceptability can be compared using standard statistical tests (4) and the decision made whether or not a particular model is significantly superior to any other. 

M-), (P-) Stereochemical descriptors (M = minus, P = plus) introduced to describe the chirality of helical molecules. Extension of the CIP system to planar chirality gave an alternative description aR/aS for helical molecules such as helicenes, aR invariably = (M) and aS = (P), but for compounds showing planar chirality the reverse, with pR = (P) and pS = (M). Best avoided. See Section 7.3.2. 

In this case, the reference axis is drawn through the metal ion in a fashion perpendicular to the chelate ring. The skew line defining the helical sense (L for left-hand, and D for right-hand) is the bond from the chelate ring to the rest of the molecule. The L and D complexes are diastereomeric and can be separated from each other for direct stereochemical studies of their individual binding and inhibitory properties. 

The loss of solubility of a protein at an interface and the observed area per residue suggested that the molecule unfolded and adopted the P conformation. This structure with intermolecular hydrogen bonds adequately accounted for the area observed and is still postulated by some workers (3). Cheesman and Davies (4) suggested other extended conformations with the orientation of the side chains largely determined by their hydrophobic or polar character. Their proposals, mainly based on early work on synthetic polypeptides, do not conform to present stereochemical criteria nor do they take account of the possibility that the a-helix or related helical conformations might be present. 

Thioredoxin from E. coli has been studied extensively using biochemical, spectroscopic and X-ray diffraction techniques. The protein consists of a single polypeptide chain of 108 amino acid residues of known sequence. The protein has been cloned and expressed. Thioredoxin of E. coli is a compact molecule with 90% of its residues in hehces, beta-strands or reverse turns. This protein transports electrons via an oxidation-reduction active disulfide". The oxidized form thioredoxin-(S2) is reduced to thioredoxin-(SH)2. In particular, this protein was found to participate in the reduction of ribonucleotides to deoxyribonucleotides. In Fig. 1, the optimized stracture is shown with a carbon backbone for clarity only. The molecule consists of two conformational domains, connected by two helices. The beta-sheet forms the core of the molecule packed on either side by clusters of hydrophobic residues. Helices form the external surface. We used a crystal stracture of the oxidized form of thioredoxin from Escherichia coli that has been refined by the stereochemically restrained least-squares procedure at 1.68 A resolution". ... 

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