Metal Binding Conservation Patterns

Not all amino acid side chains make good ligands for metal ions. Acidic residues such as aspartate and glutamate are frequently found to coordinate small metal ions like Ca2+ or Mg2+, while cysteine, histidine and aspartate are frequently involved in 

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Fig. 41. Berg s proposed structure of a zinc finger peptide (left) hydrogen bond pattern (center) ribbon diagram illustrating secondary-structure components (right) molecular model illustrating conserved metal-binding and hydrophobic residues. [Reprinted with permission from Berg, J. M. (1988) Proc. Natl. Acad. Set. U.S.A. 85, 99-102.]...

Figure 5-2. Typical conservation patterns of three protein classes. Residues invariant or conserved in more than 80% ofthe sequences are printed on a black or grey background, respectively. A Mainly nonpolar conservation in the UBA domain, a small protein domain that interacts preferentially with ubiquitin1781. B Invariant polar active site residues in the phospholipase D family1291. C Nearly invariant metal-binding residues in the HtpX/Ste24 family of Zn-containing metalloproteases.

From what was said in the previous paragraphs, it appears that the specific conservation pattern of a protein family can be used to predict whether the proteins are enzymes, bind metal ions, or rather have a structural or regulatory role. If the proteins are known to be enzymes, the conservation pattern can be used to predict which residues are part of the active site, and possibly also which catalytic mechanism is being used. For example, it would be straightforward to submit a family of structurally uncharacterized proteases to that type of analysis in order to find out whether they are serine proteases, aspartate proteases, metalloproteases, or if they belong to a different class. Moreover, it is possible to compare the family s conservation pattern with those of other, better characterized enzyme families this approach will be discussed in more detail in Sect. 5.6. 

Metallothioneins, MTs, are ubiquitous low-molecular-weight proteins high in cysteine and metal content and devoid of aromatic amino acids, encoded by a multigene family. Human MTs bind up to seven zinc atoms and contain 61—68 amino acids, of which 20 are highly conserved cysteines. In the CNS, MTs show a diverse pattern of expression with MT-1 and MT-2, mainly expressed in astrocytes and spinal glia, but largely absent from neurons, whereas MT-3 is expressed exclusively in neurons and may play an important role in neuronal zinc homeostasis as it is widely distributed in the brain associated with neurons containing synaptic zinc. 

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