Glutamate catalytic

Most such carboxylic ester hydrolases (Upases) contain a Ser-His-Aspartate/ Glutamate catalytic triad (Serl05-His224—Aspl87) in the active site, and share (at least in part) the common structural framework of the a,P-hydrolase fold. This fold is composed mainly of parallel P-sheet, flanked on both sides by a-helices [51]. A unique structural feature common to all lipases is a lid or flap composed of an amphiphilic a-helix peptide sequence which, in its closed conformation, prevents access of the substrate to the catalytic site [52]. When the lid is opened. 

Radiolabeled folate provides a powerful tool for folate bioavaHabiUty studies in animals and for diagnostic procedures in humans. Deuteration at the 3- and 5-positions of the central benzene ring of foHc acid (31) was accompHshed by catalytic debromination (47,48) or acid-cataly2ed exchange reaction (49). Alternatively, deuterium-labeled fohc acid (32) was prepared by condensing pteroic acid with commercially available labeled glutamic acid (50). 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

Peptidases have been classified by the MEROPS system since 1993 [2], which has been available viatheMEROPS database since 1996 [3]. The classification is based on sequence and structural similarities. Because peptidases are often multidomain proteins, only the domain directly involved in catalysis, and which beais the active site residues, is used in comparisons. This domain is known as the peptidase unit. Peptidases with statistically significant peptidase unit sequence similarities are included in the same family. To date 186 families of peptidase have been detected. Examples from 86 of these families are known in humans. A family is named from a letter representing the catalytic type ( A for aspartic, G for glutamic, M for metallo, C for cysteine, S for serine and T for threonine) plus a number. Examples of family names are shown in Table 1. There are 53 families of metallopeptidases (24 in human), 14 of aspartic peptidases (three of which are found in human), 62 of cysteine peptidases (19 in human), 42 of serine peptidases (17 in human), four of threonine peptidases (three in human), one of ghitamicpeptidases and nine families for which the catalytic type is unknown (one in human). It should be noted that within a family not all of the members will be peptidases. Usually non-peptidase homologues are a minority and can be easily detected because not all of the active site residues are conserved. 

Fig. 4. Proposed catalytic cycle for the hydroxylation of methane by MMO. The reductase and B components may interact with the hydroxylase in one or more steps of the cycle. Protons are shown in the step in which intermediate Q is generated, but other possibilities exist (see Fig. 3 and the text). The curved line represents a bridging glutamate carboxylate ligand.

The specificity determinants surrounding the tyrosine phospho-acceptor sites have been determined by various procedures. In PTK assays using various substrates, it was determined that glutamic residues of the N-terminal or C-terminal side of the acceptor are often preferred. The substrate specificity of PTK catalytic domains has been analyzed by peptide library screening for prediction of the optimal peptide substrates. Finally, bioinformatics has been applied to identify phospho-acceptor sites in proteins of PTKs by application of a neural network algorithm. 

Metalloenzymes with non-heme di-iron centers in which the two irons are bridged by an oxide (or a hydroxide) and carboxylate ligands (glutamate or aspartate) constitute an important class of enzymes. Two of these enzymes, methane monooxygenase (MMO) and ribonucleotide reductase (RNR) have very similar di-iron active sites, located in the subunits MMOH and R2 respectively. Despite their structural similarity, these metal centers catalyze very different chemical reactions. We have studied the enzymatic mechanisms of these enzymes to understand what determines their catalytic activity [24, 25, 39-41]. 

Surface faceting may be particularly significant in chiral heterogeneous catalysis, particularly in the N i/P-ketoester system. The adsorption of tartaric add and glutamic acid onto Ni is known to be corrosive and it is also established that modifiers are leached into solution during both the modification and the catalytic reaction [28]. The preferential formation of chiral step-kink arrangements by corrosive adsorption could lead to catalytically active and enantioselective sites at step-kinks with no requirement for the chiral modifier to be present on the surface. 

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