Substrate binding site

Figure 4.8 The active site in all a/p barrels is in a pocket formed by the loop regions that connect the carboxy ends of the p strands with the adjacent a helices, as shown schematically in (a), where only two such loops are shown, (b) A view from the top of the barrel of the active site of the enzyme RuBisCo (ribulose bisphosphate carboxylase), which is involved in CO2 fixation in plants. A substrate analog (red) binds across the barrel with the two phosphate groups, PI and P2, on opposite sides of the pocket. A number of charged side chains (blue) from different loops as welt as a Mg ion (yellow) form the substrate-binding site and provide catalytic groups. The structure of this 500 kD enzyme was determined to 2.4 A resolution in the laboratory of Carl Branden, in Uppsala, Sweden. (Adapted from an original drawing provided by Bo Furugren.)...

Inhibition of a regulatory enzyme by a feedback inhibitor does not conform to any normal inhibition pattern, and the feedback inhibitor F bears little structural similarity to A, the substrate for the regulatory enzyme. F apparently acts at a binding site distinct from the substrate-binding site. The term allosteric is apt, because F is sterically dissimilar and, moreover, acts at a site other than the site for S. Its effect is called allosteric Inhibition. 

KCOs binding site and a substrate-binding site. Protein kinases... 

Cleavage occur s at the scissile bond. Residues in the substrate towards the N-terminus are numbered PI, P2, P3, etc, whereas residues towards the C-terminus are numbered PI, P2, P3 etc. Cleavage occurs between PI and P1. For a peptidase with limited specificity, only the residue in PI or PI is important for specificity. A peptidase with an extended substrate binding site will have a preference for residues in other positions. For example cathepsin L prefers substrates with phenylalanine in P2 and arginine in PI. However, this is a preference only, and cathepsin L cleaves substrates after other amino acids. Caspase-3 has a preference for Asp in both P4 and PI, but it is unusual for substrate specificity to extend much further from the scissile bond. The peptidase with the most extended substrate specificity may be mitochondrial intermediate peptidase that removes an octopeptide targeting signal from the N-terminus of cytoplasmically synthesized proteins that are destined for import into the mitochondrial lumen. 

A second important question yet to be solved concerns the function of the Fepr protein in the organisms in which it has been found, and the mechanism by which it achieves this function. Clearly, X represents a potential substrate binding site within cluster 2, and the presence of a substrate in this position will complete the coordination of Fe5 and Fe7. The nature of X, however, remains an enigma, although... 

Ji X, Tordova M, O Donnell R, Parsons JF, Hayden JB, Gilliland GL, et al. Structnre and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione -transferase. Biochemistry 1997 36 9690-702. 

A linear form of the Hill equation is used to evaluate the cooperative substrate-binding kinetics exhibited by some multimeric enzymes. The slope n, the Hill coefficient, reflects the number, nature, and strength of the interactions of the substrate-binding sites. A... 

Fig. 6. Vectorial phosphorylation by a mechanism in which translocation and phosphorylation of the sugar are two distinct steps. The product binding site of the translocator T (domain C of II ") would be the substrate binding site of the kinase K (domains A and B). Since both the left-hand cycle and the right-hand cycle are catalyzed by the same enzyme they will very likely be kinetically dependent. Note that the kinetic cycle on the left-hand side of the figure is identical to Fig. 5.

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