Pocket of apo

Fig. 4. The lipid pocket of apo B. Apo B22.5 is represented with P-strands shown as green arrows and a-helices shown as turquoise tubes. l-Palmitoyl-2-oleoylphosphatidyIcholine (POPC) is shown with carbon atoms in gray and oxygens in red. There are 34 POPC molecules in the large opening and 14 POPC molecules in the small opening. Thus, a total of 48 POPC molecules fit into the lipid pocket. From Ref. [24], with permission. (See color plate section, plate no. 16.)...

A T-C polymorphism was described in the sequence of apo(a)-KIV10 (V6), corresponding to nucleotide 12,605 of the published cDNA sequence (M24). This variant results in the substitution of a methionine (ATG) with a threonine (ACG) at this position. No correlation was observed between the polymorphism and plasma Lp(a) levels. Although the Met-Thr substitution is present within the lysine binding pocket in KIV10, its effect on lysine binding properties of this kringle remains to be determined. 

A more complete picture of the protein-Ugand interaction is given by the docking mode of the bioactive conformation in the binding pocket of the receptor protein. In case the apo protein structure is known from NMR or... 

An important structural difference between eliminases and mutases concerns the axial base coordinated to the cobalt, perpendicular to the plane of the corrin ring. Whereas in all the eliminases, the axial base is the dimethylbenzimidazole of the coenzyme itself (Fig. 1), the mutases use a conserved histidine residue of the enzyme for this purpose. On binding of the coenzyme to the apo-enzyme, the axial base is replaced by the histidine and moves into a distinct pocket of the protein. Methyltransferases (see below) also use a protein histidine as axial base, whose reactivity is fine tuned by protonation. Possibly the mutases and methyltransferases have a common evolutionary origin, whereas the eliminases evolved separately. 

Figure 7.22. Schematic representation of apo- and holo-RXR ligand binding domain. Helices 1-12 (H1-H12) are indicated. Helices indicated in yellow and red represent the apo- and holo-forms of the receptor, respectively, whereas helices indicated in blue and green are positioned similarly in both forms of the receptor. The arrows represent movement of the helices to accommodate 9-cis-RA in the binding pocket (indicated). This figure was kindly supplied by Dr. Pascal Egea. See color insert.

Vanadate and Phosphatases. The structural similarity between vanadate and phosphate is impressively demonstrated by the fact that apo-VHPOs can exhibit some phosphatase activity, whereas certain vanadate-inhibited phosphatases exert haloperoxidase activity, a fact which roots in homologies of the active site protein pockets of both classes of enzymes, and the structural analogy of the active centers (the histidine-coordinated vanadate) in the VHPOs and the phosphatases (17) cf Fig. 2. Vanadate-inhibited phosphatases for which peroxidase activity has been reported are of bacterial Shigella flexneri, Salmonella enterica (18)) and fungal origin (ph3rtases from Aspergillus (19)). 

Figure 5. Structure of MK2(47-366, T222E) bound to a lead compound. The micromolar-potency inhibitor was soaked into a Form IV crystal. The inhibitor, represented as a tan molecular surface, binds deeply in the ATP pocket of MK2(47—366, T222E) (lainbow coloring). Apo-MK2 (PDB entry IKWP light-grey) is shown for comparison.

While no MEK apo structures have been published, comparisons to the catalytic domains of similar kinases reveal a number of differences versus the tertiary structure of MEKl. Relative to a crystal structure of PKA, there is an outward rotation of the N-terminal portion of hehx C by approximately 10 A and the formation of a short, two-turn a-hehcal segment of the activation loop. Both of these changes give rise to the allosteric binding pocket which enables the unique binding mode. Inhibitors such as PD318088 stabi-... 

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