Oxy anion hole

Whiting AK, Peticolas WL (1994) Biochemistry 33 552-561 Selected reference with emphasis on the LBHB character of serine proteases oxy anion hole... 

According to this model, the action of the peptide catalysts used in the Julid-Colonna epoxidation bears a lot of similarity to that of enzymes, in particular the binding/activation and proper orientation of the substrates which ultimately effects the excellent enantioselectiv-ities in the overall process. In fact, the H-bonding motif discovered as the catalytically active site also acts as the oxy-anion hole in serine esterases and is known to bind/stabilize a variety of fully or partially negatively charged entities (Milner-White and Watson 2002a,b), the P-hydroperoxyenolate, in the present case. Studies by Roberts, Kelly,... 

Of course there are other binding sites possible through which GSK-3 3 could be inhibited other than the ATP site. One such low-affinity cation binding site is discussed below with respect to inhibition by the lithium ion. It has recently been suggested that thiadiazolidinone structures may be binding in an oxy-anion hole close to the activation loop (discussed in detail below). Furthermore, inhibition can be achieved by inhibition of substrate binding (such... 

Other mechanisms are also consistent with this structure, including a cyclic four-membered transition state for a concerted reaction in which the bond forming reactions at carbons-2 and -3 are asynchronous, thereby allowing partial anionic charge to be localized on the carbonyl oxygen which it can be stabilized by the oxy-anion hole. 

This epoxidation proceeds by conjugate addition of hydroperoxide anion followed by cyclisation of the resulting enolate in similar fashion to the Wietz-Scheffer process. It is proposed that the polyamino acid, present as an a—helix, forms a simple active site near the N-terminus within which the epoxidation occurs, and that catalysis arises from stabilisation of the intermediate enolate by interaction with an oxy-anion hole formed within this active site. 

This three point binding mode implies that the chirality of the helix determines the asymmetric induction of the epoxidation and not the chirality of the or-carbon atoms of the peptide catalyst. " Natural enzymes show related arrangements of three NHs as binding motif for fully or partially negatively charged entities. The oxy-anion hole in serine esterase is known to use a similar H-bonding motif as proposed in this model. ... 

The tetrahedral intermediate is stabilized by hydrogen bonding in a pocket that is called the oxy-anion hole. Amide NHs from the peptide backbone contribute the hydrogen bonding donors. 

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