Small-molecule substrates

This enzyme [EC 3.4.22.25] catalyzes the hydrolysis of peptide bonds with a preference for Gly-Xaa in proteins and small molecule substrates. The enzyme, a member of the peptidase family Cl, is isolated from the papaya plant, Carica papaya. It is not inhibited by chicken cys-tatin, unlike most other homologs of papain. 

Fig. 7.24 Layer-by layer assembly of dendrimer-based films arising from host-guest interactions between cyclodex-trin and small-molecule substrate-functionalized dendri-...

Prompt fluorescence with small molecule substrates (DiFMUP, AnaSpec Sensolyte) Action of enzyme on substrate converts substrate into fluorescent compound excellent substrates available for phosphatases Versatile very strong signal Requires highly purified enzymes, or contaminating phosphatases can be deceptive Watanabe (1998) Johnston (2007) Montalibet (2005)... 

Phosphatase enzyme essays most commonly employ artificial small molecule substrates that become fluorescent by removal of the phosphate moiety. Other methodologies similar to those employed in kinase assays can also be used, in which the removal of phosphate from a peptide or protein substrate can be detected. Figure 1.1 shows the basic principles. Many commercially available kits and published references describe these methodologies (Table 1.1). 

The properties of the lanthanide elements and their organometallic complexes described in the previous section explain in part why organo-met lic chemists in the past found lanthanide chemistry much less interesting than transition metal chemistry. The highly ionic, trivalent organolanthanide complexes appeared to have little potential to interact with the small-molecule substrates that provide such a rich chemistry for the transition metals neutral unsaturated hydrocarbons, H2, CO, phosphines, etc. The two-electron oxidation reduction cycles so important in catalytic transition metal chemistry in 18 16 electron complexes seemed... 

Pathway Tools conceptualizes the metabolic network in three layers. The first layer consists of the small-molecule substrates on which the metabolism operates. The second layer consists of the reactions that interconvert the small-molecule metabolites. The third layer is the metabolic pathways in which the components are the metabolic reactions of the second layer. Note that not all reactions in the second layer are included in pathways in the third layer because some metabolic reactions are not assigned to any metabolic pathway. 

Ehmann DE, Trauger JW, Stachelhaus T, Walsh CT. Aminoacyl-SNACs as small-molecule substrates for the condensation domains of nonribosomal peptide synthetases. Chem. Biol. 2000 7 765-772. Sieber SA, Tao J, Walsh CT, Marahiel MA. Peptidyl thiophenols as substrates for nonribosomal peptide cyclases. Angew. Chem. Int. Ed. Engl. 2004 43 493-498. 

Binding of small antigens, e.g., haptens, to antibodies occurs when hypervariable region amino acid residues form a pocket into which the hapten fits. Such binding is similar to that between enzymes and small-molecule substrates, i.e., a lock-and-key fit between antigen and... 

Circular dlchrolsm studies of proteins and nucleic acids are providing useful data on conformations in solution and their modification by various agents. Studies of the binding of N-acetylglucosamine to egg-white lysozyme and of acetazolamide to human carbonic anhydrase exemplify the application of this technique to the measurement of conformational changes induced in enzymes by small molecule substrates and inhibitors. 

Note, that in the case of bismuth the growth of upright oriented pentacene molecules has been observed - even in the very first monolayer [47]. This orientation has been explained [47] by the rather small density of states near the Fermi level of this semi-metal leading to a rather small molecule-substrate interaction which becomes comparable or even weaker than the mutual molecular interaction and thus parallels the situation observed for pentacene deposited on inert substrates such as Si02 [48]. 

In addition to forming functional nanocomposites and optical materials, LLC systems also have value in the area of catalysis. LLC phases have a number of features that make them amenable for accelerating chemical reaction rates. For example, LLC phases have regular nanometer-scale water- or polar solvent-filled cavities and hydrophobic domains of uniform size that are close in size to typical small molecule substrates. These domains can afford confined environments to encapsulate reactants and catalytic entities, thereby increasing their local concentration and the probability of productive colli-... 

Rathore R, Coir JJ, Lebre DT, Seibel WL, Greis KD (2009) Extending matrix-assisted laser desorption/ionization triple quadrupole mass spectrometry enzyme screening assays to targets with small molecule substrates. Rapid Commun Mass Spectrom 23 3293-3300... 

Broad specificity for cleavage of proteins, but strong preference for Z-Arg-Arg-l-NHMec amongst small molecule substrates. 

The structural basis for recognition of protein substrates is not yet clear. However, structures of PAD4 in complex with A -benzoyl-L-arginine amide and peptides from histones H3 and H4 that are known to he citrullinated have provided clues as to how PAD4 hinds and recognizes small molecule substrates. As with ADI and DDAH, the arginine residue of the substrate binds at the center of the propeller of the catalytic domain, and the conserved core residues interact with the guanidine side chain. ... 

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