Amino acid residues invariant

The electron transport protein, cytochrome c, found in the mitochondria of all eukaryotic organisms, provides the best-studied example of homology. The polypeptide chain of cytochrome c from most species contains slightly more than 100 amino acids and has a molecular weight of about 12.5 kD. Amino acid sequencing of cytochrome c from more than 40 different species has revealed that there are 28 positions in the polypeptide chain where the same amino acid residues are always found (Figure 5.27). These invariant residues apparently serve roles crucial to the biological function of this protein, and thus substitutions of other amino acids at these positions cannot be tolerated. 

Neurotoxins present in sea snake venoms are summarized. All sea snake venoms are extremely toxic, with low LD5Q values. Most sea snake neurotoxins consist of only 60-62 amino acid residues with 4 disulOde bonds, while some consist of 70 amino acids with 5 disulfide bonds. The origin of toxicity is due to the attachment of 2 neurotoxin molecules to 2 a subunits of an acetylcholine receptor that is composed of a2 6 subunits. The complete structure of several of the sea snake neurotoxins have been worked out. Through chemical modification studies the invariant tryptophan and tyrosine residues of post-synaptic neurotoxins were shown to be of a critical nature to the toxicity function of the molecule. Lysine and arginine are also believed to be important. Other marine vertebrate venoms are not well known. 

Oxidative bleaching of wool is invariably carried out with hydrogen peroxide. The active species involved is likely to be the same as on cellulosic substrates but specific reactions with wool amino acid residues must be considered. The primary reaction is oxidation of cystine disulphide bonds leading to the formation of cysteic acid residues (Scheme 10.41). The rupture of disulphide crosslinks, with attendant increase in urea-bisulphite and alkali solubility values, adversely affects fibre properties. As the severity of bleaching conditions increases, the urea-bisulphite solubility remains little changed but the relationships between alkali solubility and cysteic acid (Figure 10.36) and between cystine and cysteic acid (Figure... 

In the third model (2, right), the colored residues are those that are located on the surface and occur invariably (red) or almost invariably (orange) in all known insulins. It is assumed that amino acid residues that are not replaced by other residues during the course of evolution are essential for the protein s function. In the case of insulin, almost all of these residues are located on one side of the molecule. They are probably involved in the binding of the hormone to its receptor (see p.224). 

Antimicrobial peptides are also an integral part of mammalian cell-mediated immunity. They are produced by phagocytic cells, particularly neutrophils, and are designate defensins (47). Althou defensin molecules from humans, guinea pigs, rabbits, and rats may vary between 29-34 amino acid residues and differ slightly in sequence, they invariably show conservation in sue cysteine residues which are required for a defmed pattern of disulfide bonds (47). 

Signal sequences usually occur at the amino terminus of polypeptides to be transported. These sequences vary in length from 10 to 40 amino acid residues and are generally characterized by the occurrence of a block of hydrophobic residues. The presence of hydrophobic residues reflects the fact that protein transport invariably involves the movement of proteins across lipid membranes. The hydrophobic residues both target the protein to the appropriate compartment and initiate penetration into the membrane. 

Cytochromes c from different species contain the same heme group but may differ in the nature of the amino acid residues at various positions of the polypeptide chain. The functional importance of those segments of the protein which are invariant among different species has long been recognized (Margoliash and Schejter (71)). The NMR spectra in the reduced and oxidized forms indicate that methionine is an axial ligand in all the mammalian-type cytochromes c studied so far (McDonald et al. (79) Wuthrich (111)). 

Fig. 5-24. Schematic model of sub-unit II of cytochrome oxidase. 1 vo hydrophobic helices anchor the sub-unit to the membrane. The CuA binding site is indicated in a location outside the membrane close to the COOH-terminal end of the peptide. Invariant amino acid residues are shown. Reproduced from Holm et al. (1987).

Chavkin and Goldstein [3] pointed out that endogenous opioid peptides conform to a message-address motif, and it was suggested that the invariant tetrapeptide sequence Tyr-Gly-Gly-Phe can be viewed as the message while subsequent amino acid residues constitute the address. A modification of this... 

The sequences have been derived from references referred to in the text. Two examples of enzymes from the amylase family are shown for comparison. Over 40 enzymes ranging from amylases, glucosidases, various a-1,6-debranching enzymes, and 4 examples of branching enzymes have been compared by Svensson.286 The invariant amino acid residues believed to be involved in catalysis are in bold letters)... 

X-ray crystal structure studies of influenza A/N2, A/N9, and B sialidases bound with a-Neu5Ac [66] show that the active site contains 18 invariant amino acid residues that either interact with the bound a-Neu5Ac or support these residues. These residues are conserved in all strains of influenza A and B viruses, suggesting their involvement in the enzymatic activity [65,66], The residues helped define the topology of the active site [66, 67], Of those conserved amino acids interacting with the substrate, many are polar, but there are also a number of nonpolar residues... 

In this sequence, which amino acid residues are invariant (conserved across all species) ... 

The synthetic [2Fe-2S] model complex of the 20-peptide complex exhibits two LMCT absorption maxima at 423 and 461 nm in DMF, maxima which are near to those of the native plant-type ferredoxin (423 and 466 nm) (69). Two redox couples for — 3/—2 were observed at — 0.64 V versus SCE and at —0.96 V versus SCE in DMF. One of them is very close to the value (—0.64 V versus SCE) of native ferredoxin. The 20-peptide complex containing invariant sequences Cys-A-B-C-D-Cys-X-Y-Cys and Leu-Thr-Cys-Val possesses all essential factors for a model of the active site except for the peptide conformation. The positive-shifted redox potential of the 20-peptide complex in DMF is undoubtedly due to the interactions between the Fe2S22+ core and adjacent amino-acid residues, giving rise to NH--S hydrogen bonding. 

Fig. 2. Ribbon model of the three-dimensional structure of the PapD chaperone. The consensus sequence for twelve members of the family was superimposed on the tertiary structure of PapD. The position of the invariant amino acid residues is shown in black, and that of the residues conserved in at least eight of the sequences, in gray.

A catalytic system formed by Thr-1, Glu-17 and Lys-33 has been defined in the T. addophilum proteasome by structural and mutational studies. Close to Thr-1 are residues Ser-129, Ser-169 and Asp-166, which seem to be required for the structural integrity of the site but may also be involved in catalysis. These residues are invariant in the active subunits. The structure of the active sites of the bovine proteasome were compared by superimposing the functional amino acid residues Thr-1, Glu-17, Arg-19, Lys-33, Ser-129, Asp-166, Ser-169 and Gly-170. Root mean square (R.m.s.) deviations for all atoms of these functional residues in the active bovine subunit pairs p -p2, y l-y 5, and p2 ps were 0.4 A, 0.3 A and 0.4 A, respectively, demonstrating that the functional core of each active subunit is well conserved. 

This group of enzymes share a eonserved domain comprising about 100 amino acid residues that contains the following invariant ifinger printi residues, although there are several additional positions where the side-chain character is conserved (Figure 7). 

Conserved or Invariant Amino Acid Residues among Class 11II Secretory Phospholipases A ... 

Aligned Albumin Sequences Illustrating Conserved Amino Acids and Invariant Residues" SEQUENCE HOMOLOGY HUMAN/BOVINE/EQUINE/OVIMB/RAT/PROG/SAUmN... 

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