Catalyst-substrate binding

Figure 13 Structures of PTPs include two important motifs, the P-loop that bears the cysteine nucleophile within the general signature motif (H/V)Cp<)5R(S/T), and the WPD-loop, which includes an important aspartic acid, a general acid-base catalyst. Substrate binding by the P-loop promotes a change of the WPD-loop conformation from an open, inactive to a closed, active conformation in which the aspartic acid completes the catalytic ensemble used for catalysis. The representation in this figure was created using PyMol from the PTP1B structures in apo-bound (PDB 2CM2) and inhibitor-bound (PDB 1BZJ) forms.

The WPD loop is a flexible /3-turn found in all tyrosine-specific PTPs, and includes the conserved aspartic acid residue that serves as a general acid-base catalyst. Substrate binding thermodynamically favors the closed, catalytically active conformation, where the aspartic acid is in position for catalysis (Figure 15). The DSPs also share a conserved aspartic acid in this catalytic role. However, except for VHZ, a recently purified DSP which may possess a flexible IPD loop, the aspartic acid in DSPs is located on a rigid structure. Consequently, no conformational change analogous to WPD loop movement in PTPs seems to be associated with catalysis for most DSPs. 

Controi of catalyst-substrate binding geometry steric shielding of stereotopic faces of the acceptor... 

Ca.ta.lysis, Iridium compounds do not have industrial appHcations as catalysts. However, these compounds have been studied to model fundamental catalytic steps (174), such as substrate binding of unsaturated molecules and dioxygen oxidative addition of hydrogen, alkyl haHdes, and the carbon—hydrogen bond reductive elimination and important metal-centered transformations such as carbonylation, -elimination, CO reduction, and... 

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

Lewis-Acid Catalyzed. Recently, various Lewis acids have been examined as catalyst for the aldol reaction. In the presence of complexes of zinc with aminoesters or aminoalcohols, the dehydration can be avoided and the aldol addition becomes essentially quantitative (Eq. 8.97).245 A microporous coordination polymer obtained by treating anthracene- is (resorcinol) with La(0/Pr)3 possesses catalytic activity for ketone enolization and aldol reactions in pure water at neutral pH.246 The La network is stable against hydrolysis and maintains microporosity and reversible substrate binding that mimicked an enzyme. Zn complexes of proline, lysine, and arginine were found to be efficient catalysts for the aldol addition of p-nitrobenzaldehyde and acetone in an aqueous medium to give quantitative yields and the enantiomeric excesses were up to 56% with 5 mol% of the catalysts at room temperature.247... 

An essential step in processes utilizing soluble transition metal catalysts is the coordination of the substrate to the transition metal (5.). A corequisite is the availability of a vacant site in the coordination sphere of the metal for substrate binding, a provision often met by dissociation of a bonded... 

For hydrogenation to take place, the substrate usually needs to bind to the metal complex, although exceptions are known to this rule [25]. Substrate inhibition can occur in a number of ways, for example if more than one molecule of substrate binds to the metal complex. At low concentration this may be a minor species, whereas at high substrate concentration this may be the only species. One example of this is the hydrogenation of allyl alcohol using Wilkinson s catalyst. Here, the rate dependence on the substrate concentration went through a maximum at 1.2 mmol IT1. The authors propose that this is caused by formation of a complex containing two molecules of allyl alcohol (Scheme 44.1) [26],... 

For a poly- or oligonucleotide catalyst-substrate interaction the problem of binding-specificity is in principle solved simply by using the complementary sequence, and chemistry based on classical... 

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