Structurally invariant residues

From a comparison of the primary structure of the neurotoxins, Karlsson (11) and Ryden et al. (12) observed that certain invariant amino acid positions in the structural chain are important for the general folding of the molecule, while others are important for the neurotoxic activity. The former are called structurally invariant residues, whereas the later are called functionally invariant residues. 

Figure 13.14 (a) Schematic diagram of the main chain and four almost invariant residues of the fourth WD repeat of Gp from transducin. The view is roughly perpendicular to the central tunnel and the plane of the sheet. The red stripes denote hydrogen bonds, (b) Schematic view of two WD repeats illustrating the structural relationships between two consecutive repeats. The first repeat is brown and the second repeat is orange. The positions of the four almost invariant residues in the first repeat are circled. (Adapted from J. Sondek et al., Nature 379 369-374, 1996.)... 

NP2. In particular, Tyr82 flips from outside the protein in NP1/NP4, where it contacts bulk solvent, to inside the protein in NP2, where it hydrogen bonds to Glu55 (110). Thus, modeling the NP2 structure based on those of NPl and NP4, and, as is normally done, keeping the invariant residues structurally conserved, would lead to errors. Structures of protein families such as the nitrophorins therefore provide key information for the future improvement of structure prediction and structural genomics. 

Crystals of pronase-released heads of the N2 human strains of A/Tokyo/3/67 [44] and A/RI/5+/57 were used for an x-ray structure determination. The x-ray 3-dimensional molecular structure of neuraminidase heads was determined [45] for these two N2 subtypes by a novel technique of molecular electron density averaging from two different crystal systems, using a combination of multiple isomorphous replacement and noncrystallographic symmetry averaging. The structure of A/Tokyo/3/67 N2 has been refined [46] to 2.2 A as has the structures of two avian N9 subtypes [47-49]. Three influenza type structures [50] have also been determined and found to have an identical fold with 60 residues (including 16 conserved cysteine residues) being invariant. Bacterial sialidases from salmonella [51] and cholera [52] have homologous structures to influenza neuraminidase, but few of the residues are structurally invariant. 

Fig. (4). The primary structures of enod40 peptides. Enod40 peptides are compared from legumes with determinate nodules (a), legumes with indeterminate nodules (b), and non-legumes (c). Gaps (-) were introduce to optimize the alignment. The invariant residues are shown in bold face. The figure was modified after [79],...

Fig. 3. Periplasmic pilus chaperone consensus sequence. Amino acid sequence of the PapD chaperone (top line) and consensus sequence derived from the comparison of twelve chaperones (second line). Amino acids are indicated using the one-letter code. In the consensus sequence, a letter shows a residue that is present in at least eight out of twelve sequences, an asterisk designates an invariant residue, and a box shows a position with a hydrophobic residue in all twelve periplasmic chaperones. The arrows underneath the sequence represent the /3 strands found in the PapD structure.

Fig. 2. Summary of structural features of C-type animal lectins. The (nearly) invariant residues found in the coimnon carbohydrate-recognition domain of the C-type lectins are shown, flanked by schematic diagrams of the special effector domains (if any) found in individual members of the family. GAG, glycosaminoglycan EGF, epidermal growth factor. Reproduced from K. Drickamer, Two Distinct Classes of Car bohydrate-recognition Domains in Animal Lectins, J. Biol. Chem., 263 (1988) 9557-9560 (Ref. 35) 1988. The American SocietyforBiochemistry Molecular Biology with permission by Professor Kurt Drickamer and The American Society for Biochemistry Molecular Biology.

There are nine invariant residues in the plant peroxidase superfamily 28). Five of these are involved in catalysis and are shown in Fig. 2 for CCP. The other conserved residues play important structural roles, such as a buried salt bridge between AsplOG and Argl30 (CCP numbering) 28). 

In every enzyme family and superfamily, there are invariant residues that are required to maintain structure and/or function. However, for the majority of the residues, considerable variability is tolerated enzymes with <30% sequence identity often have very similar structures and identical functions. Such sequence divergence occurs by neutral drift, a process by which mutations that do not affect the fitness of the organism accumulate over long periods of time. 

At the dimer interface Gly-51 and Gly-114 are invariant residues that form hydrogen bonds with the nonconserved residue at position 151 Cys-57 and Cys-146 form a disulfide bridge stabilizing a region of the protein structure involved in monomer/monomer contact (see Section II). Four invariant residues, two Gly (16 and 147), one Phe (45), and one Leu (106) seem to contribute to maintaining the stable Greek key )8-barrel fold (see Section II). 

---