Aspartate structure

The side chains of the 20 different amino acids listed in Panel 1.1 (pp. 6-7) have very different chemical properties and are utilized for a wide variety of biological functions. However, their chemical versatility is not unlimited, and for some functions metal atoms are more suitable and more efficient. Electron-transfer reactions are an important example. Fortunately the side chains of histidine, cysteine, aspartic acid, and glutamic acid are excellent metal ligands, and a fairly large number of proteins have recruited metal atoms as intrinsic parts of their structures among the frequently used metals are iron, zinc, magnesium, and calcium. Several metallo proteins are discussed in detail in later chapters and it suffices here to mention briefly a few examples of iron and zinc proteins. 

Figure 2.11 Beta sheets are usuaiiy represented simply by arrows in topology diagrams that show both the direction of each (3 strand and the way the strands are connected to each other along the polypeptide chain. Such topology diagrams are here compared with more elaborate schematic diagrams for different types of (3 sheets, (a) Four strands. Antiparallel (3 sheet in one domain of the enzyme aspartate transcarbamoylase. The structure of this enzyme has been determined to 2.8 A resolution in the laboratory of William Lipscomb, Harvard University, (b) Five strands. Parallel (3 sheet in the redox protein flavodoxin, the structure of which has been determined to 1.8 A resolution in the laboratory of Martha Ludwig, University of Michigan, (c) Eight strands. Antiparallel barrel in the electron carrier plastocyanln. This Is a closed barrel where the sheet is folded such that (3 strands 2 and 8 are adjacent. The structure has been determined to 1.6 A resolution in the laboratory of Hans Freeman in Sydney, Australia. (Adapted from J. Richardson.)...

Gouaux, J.E., Lipscomb, W.N. Crystal structures of phosphonoacetamide ligated T and phosphono-acetamide and malonate ligated R states of aspartate carbamoyltransferase at 2.8 A resolution and neutral pH. Biochemistry 29 389-402, 1990. 

The HIV-l protease is a remarkable viral imitation of mammalian aspartic proteases It is a dimer of identical subunits that mimics the two-lobed monomeric structure of pepsin and other aspartic proteases. The HIV-l protease subunits are 99-residue polypeptides that are homologous with the individual domains of the monomeric proteases. Structures determined by X-ray diffraction studies reveal that the active site of HIV-l protease is formed at the interface of the homodimer and consists of two aspartate residues, designated Asp and Asp one contributed by each subunit (Figure 16.29). In the homodimer, the active site is covered by two identical flaps, one from each subunit, in contrast to the monomeric aspartic proteases, which possess only a single active-site flap. 

The 20 common amino acids can be further classified as neutral, acidic, or basic, depending on the structure of their side chains. Fifteen of the twenty have neutral side chains, two (aspartic acid and glutamic acid) have an extra carboxylic acid function in their side chains, and three (lysine, arginine, and histidine) have basic amino groups in their side chains. Note that both cysteine (a thiol) and tyrosine (a phenol), although usually classified as neutral amino acids, nevertheless have weakly acidic side chains that can be deprotonated in strongly basic solution. 

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. 

Human insulin is derived from a biosynthetic process using strains of Escherichia coli (recombinant DNA, rDNA). Human insulin appears to cause fewer allergic reactions than does insulin obtained from animal sources. Insulin analogy, insulin lispro, and insulin aspart are newer forms of human insulin made by using recombinant DNA technology and are structurally similar to human insulin. 

The elucidation of the X-ray structure of chymotrypsin (Ref. 1) and in a later stage of subtilisin (Ref. 2) revealed an active site with three crucial groups (Fig. 7.1)-the active serine, a neighboring histidine, and a buried aspartic acid. These three residues are frequently called the catalytic triad, and are designated here as Aspc Hisc Serc (where c indicates a catalytic residue). The identification of the location of the active-site groups and intense biochemical studies led to several mechanistic proposals for the action of serine proteases (see, for example, Refs. 1 and 2). However, it appears that without some way of translating the structural information to reaction-potential surfaces it is hard to discriminate between different alternative mechanisms. Thus it is instructive to use the procedure introduced in previous chapters and to examine the feasibility of different... 

Amino acids, 109,110,214 Aspartic acid, structure of, 110 Atomic orbitals, 2-3,5 Atoms, 2-4, 15. See also Atomic orbitals degrees of freedom of, 78 free energy of changing charge of, 82 Autocorrelation functions ... 

The primary structure of a protein is the sequence of residues in the peptide chain. Aspartame consists of phenylalanine (Phe) and aspartic acid (Asp), and so its primary structure is Phe-Asp. Three fragments of the primary structure of human hemoglobin are... 

The lipase (PAL) used in these studies is a hydrolase having the usual catalytic triad composed of aspartate, histidine, and serine [42] (Figure 2.6). Stereoselectivity is determined in the first step, which involves the formation of the oxyanion. Unfortunately, X-ray structural characterization of the (S)- and (J )-selective mutants are not available. However, consideration of the crystal structure of the WT lipase [42] is in itself illuminating. Surprisingly, it turned out that many of the mutants have amino acid exchanges remote from the active site [8,22,40]. 

Fig. 1 A ribbon diagram of the crystal structure of a substrate complex of the homo-dimer HIV-1 protease (lkj7) (Prabu-Jeyabalan et al. 2002), Each monomer is shown in cyan and pink the substrate is shown in green, and the catalytic aspartic acids are highlighted in yellow...

Before analyzing in detail the conformational behaviour of y9-peptides, it is instructive to look back into the origins and the context of this discovery. The possi-bihty that a peptide chain consisting exclusively of y9-amino acid residues may adopt a defined secondary structure was raised in a long series of studies which began some 40 years ago, on y9-amino acid homopolymers (nylon-3 type polymers), such as poly(/9-alanine) 3 [14, 15], poly(y9-aminobutanoic acid) 4 [16-18], poly(a-dialkyl-/9-aminopropanoic acid) 5 ]19], poly(y9-L-aspartic acid) 6 ]20, 21], and poly-(a-alkyl-/9-L-aspartate) 7 [22-36] (Fig. 2.1). 

Fig. 2.2 Most favored helical structures proposed for two crystal forms of poly(a-n-butyl-/ -L-aspartate) (7, R=Bu) [28]. (A) Model of a (P)-3.25i4-helix. (B) Model of a (P)-4is-helix...

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