Substitution conservative

Prolactin-Like Proteins. A number of prolactin-like proteins (PLPs), which ate distinct from the PLs, have been identified in mminants and rodents (11,23). Several cDNA transcripts coding for PLPs in catde have been identified (23). These transcripts code for proteins which possess about 40% sequence homology with bovine PRL 60% if conservative substitutions ate considered. Three glycosylated PLPs, ie, PLP-A, -B, and -C, ate produced during pregnancy in the rat (11). Two additional prolactin-related molecules have been identified in the mouse (24,25), ie, proliferin [92769-12-5] (PLF) and PLF-related protein [98724-27-7]. These ate not found in other rodents and may be unique to the mouse. The functional roles of PLPs remain to be deterrnined. 

Figure 1. Most cx)mmon (consensus) sequences of the two types of sea anemone toxins. Bold letters represent residues which both toxin types have in common. Letters above each sequence are nonconservative substitutions, while letters below each sequence are conservative substitutions. A nonconservative substitution was defined as one in which (a) electronic charge changed, (b) a hydrogen-bonding group was introduced or removed, (c) the molecular size of the sidechain was changed by at least 50%, or (d) the secondary structure propensity was changed drastically from b to h or vice versa (Ref.

Fig. 11.2. Schematic representation of the primary structure of secreted AChE B of N. brasiliensis in comparison with that of Torpedo californica, for which the three-dimensional structure has been resolved. The residues in the catalytic triad (Ser-His-Glu) are depicted with an asterisk, and the position of cysteine residues and the predicted intramolecular disulphide bonding pattern common to cholinesterases is indicated. An insertion of 17 amino acids relative to the Torpedo sequence, which would predict a novel loop at the molecular surface, is marked with a black box. The 14 aromatic residues lining the active-site gorge of the Torpedo enzyme are illustrated. Identical residues in the nematode enzyme are indicated in plain text, conservative substitutions are boxed, and non-conservative substitutions are circled. The amino acid sequence of AChE C is 90% identical to AChE B, and differs only in the features illustrated in that Thr-70 is substituted by Ser.

From 13 completed amino-acid sequences and 54 partial sequences (>40 residues) of plastocyanins from higher plants it appears that sixty residues are invariant and 7 are conservatively substituted 02,7). With three algal plastocyanins included there are 39 invariant or conservatively substituted groups. It is believed that the same structural features apply to the whole family, and that highly conserved residues are an indication of functional sites on the protein surface. The upper hydrophobic and right-hand-side surfaces are believed to be particularly relevant in this context, the latter including four consecutive... 

As a consequence, the gradient of the objective function and the Jacobian matrix of the constraints in the nonlinear programming problem cannot be determined analytically. Finite difference substitutes as discussed in Section 8.10 had to be used. To be conservative, substitutes for derivatives were computed as suggested by Curtis and Reid (1974). They estimated the ratio /x of the truncation error to the roundoff error in the central difference formula... 

Fig. 12.2. Alignment of some representative members of the various classes of UBA-like domains. Positions invariant or conservatively substituted in at least 40% of the sequences are shown on black and gray background, respectively. The UBA-like domain classes are...

Fig. 3. Comparison of the amino acid sequences predicted from the a- and j3-tubulin mRNA sequences. Open circles indicate homologous, conservative substitutions, and boxed regions indicate areas of high homology. For completeness, the sequence of the first 25 amino acids of chick brain a-tubulin, deduced by the work of Luduena and Woodward (1973), is also included. Note that the asterisks indicate identical amino acids common to both polypeptide chain sequences. [Reproduced from Valenzuela et al. (1981). Nature (London) 289, 650-655.]...

Figure 7. N-terminal sequence for the first 47 amino acids of the manganese peroxidase (MnP) isolated from L. edodes cultures own on a commercial wood medium and homology with the deduced amino acid sequences for the MnP s or lignin peroxidases (LP s) reported from P. chrysosporium. Boxed areas show regions of sequence identity. Homology is the total length of identical or conservative substitutions. (Reproduced with permission from ref. 15. Copyright 1990 Springer-Verlag.)...

Figure 2. Multiple sequence alignments of the Catalytic domain family 1. As with catalytic domain analysis, these alignments were calculated using the program Clustal (10), Identities in all sequences of the group are indicated by an while conservative substitutions in all members of the alignment are indicated by a...

Structural aligmnent of IL-la, IL-ip, and IL-lRa. Residue numbering is taken from IL-ip. Residues bordered in black axe conserved over the three molecules while those in gray constitute a conservative substitution. Arrows indicate sheet region, and the cylinders... 

Figure 1 Comparison of the CGRP family peptides. The amino acids are annotated in the following way small and hydrophobic in plain text, acidic in bold, basic in bold italics and hydroxyl or amine in italics. Indicates identical or conserved residues in all peptides indicates conserved substitutions and indicates semi-conserved substitutions.

Identical amino acids are often inadequate to identify related proteins or, more importantly, to determine how closely related the proteins are on an evolutionary time scale. A more useful analysis includes a consideration of the chemical properties of substituted amino acids. When amino acid substitutions are found within a protein family, many of the differences may be conservative—that is, an amino acid residue is replaced by a residue having similar chemical properties. For example, a Glu residue may substitute in one family member for the Asp residue found in another both amino acids are negatively charged. Such a conservative substitution should logically garner a higher score in a sequence alignment than does a nonconservative substitution, such as the replacement of the Asp residue with a hydrophobic Phe residue. 

Fig-i Structural considerations about drug binding in the Kvl.5 channel pore. Amino acid sequence comparison of alpha subunit sequences from human Kvl.1-1.6 and Kv2.1, Kvll.l (hERG), Kv7.1 (KvLQTl). Symbols indicate complete amino acid conservation ( ), conservative substitution among all aligned sequences ( ), and critical substitution in a generally conserved position (.)... 

ExchangeGroup 6 Conservative Substitution HRK DENQ (C) STPAG MILV FYWJ ... 

The first basic tenet of protein-structure prediction is that the amino acid sequence, the primary structure, contains all of the information required for the correct folding of the polymer chain. This is a first approximation which clearly ignores the role of environment on the induction of structure or the action of chaperone proteins which assist the in vivo folding process. The wide variety of structural motifs that have been observed for proteins is derived from only twenty different monomers (amino acids), many of which are structurally quite similar (i.e., isoleucine and leucine vary only in branching of the butyl side chain). However, there are many cases in which the substitution of amino acids with structurally similar residues (so-called conservative substitution) will lead to a protein that will not properly fold. Studies involving deletion of even small portions of the termini of the protein sequence provide similar results. On the other hand there are proteins related through evolution with as little as 20% sequence identity which adopt similar three-dimensional structures. Therefore the information encoded in the primary sequence is specific for one protein fold, however, there are numerous other sequences, only remotely related at first glance, which will produce the same fold. 

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