‘Molecular sandwiches’ as a basis for structural and functional similarities of interferons, MSH, ACTH, LHRH, myelin basic protein, and albumins

Root‐Bernstein, Robert

doi:10.1016/0014-5793(84)80247-1

Cited by 13 publications

(3 citation statements)

References 35 publications

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“…Logically, acetylcholine should therefore bind to bungarotoxin-a testable prediction that might help to unravel the mysteries of non-peptide receptor evolution. Similarly, my laboratory has found that indoleamines bind specifically to a set of structurally related peptides (Root-Bernstein, 1984), including a short region of myelin basic protein, ACTH, and LHRH (Root-Bernstein and Westall, 1984;Takeuchi et al, 1990). Catecholamines, in contrast, bind to a very different set of peptides, including endorphins, enkaphalins, substance P (Root-Bernstein, 1987), and neurotensin (Schenk et al, 1991).…”

Section: Implications Of Complementarity Theories Of Receptor Evolutionmentioning

confidence: 96%

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Root‐Bernstein¹

2005

J. Mol. Recognit.

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This paper reviews the three major theories of peptide receptor evolution: (1) Dwyer's theory that peptide receptors evolved from self-aggregating peptides; (2) Root-Bernstein's theory that peptide receptors evolved from functionally and structurally complementary peptides; and (3) Blalock's theory that receptors evolved from hydropathically complementary sequences encoded in the antisense strand of the DNA encoding each peptide. The evidence to date suggests that the co-yevolution of peptides and their receptors is strongly constrained by one or more of these physicochemically based mechanisms, which argues against a random or frozen accident' model. The data also suggest that structure and function are integrally related from the earliest steps of receptor-ligand evolution so that peptide functionality is non-random and highly conserved in its origin. The result is a molecular paleontology' that reveals the evolutionary constraints that shaped the interaction of structure and function.

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Section: Implications Of Complementarity Theories Of Receptor Evolutionmentioning

confidence: 96%

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Root‐Bernstein¹

2005

J. Mol. Recognit.

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“…Peptides hormones and neurotransmitters, such as adrenocorticotropic hormone, luteinizing hormone releasing hormone, substance P, the enkephalins and endorphins, etc., often contain sequences of amino acids that include pairs of adjacent aromatic side chains. When any pair of the side chains tryptophan, phenylalanine, tyrosine, or histamine, is separated by a single amino acid in a linear sequence, then they can form a "molecular sandwich" of exactly the appropriate dimensions for the intercalation of another aromatic molecule [30]. If a peptide forms an alpha helix, then a pair of aromatic residues that are separated by three others will also be brought into juxtaposition to form a molecular sandwich.…”

Section: Peptide-monoamine Complexesmentioning

confidence: 99%

Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies

Root‐Bernstein¹,

Dillon²

2008

CPD

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Many examples of specific binding between small molecules are known that are associated with modified physiological and pharmacological activities. Conversely, the antagonism or synergism of small molecules is often correlated with specific binding between the molecules. It follows that small molecule binding can be used as a relatively quick, easy, and specific screen for functionally useful drug actions and interactions. These actions and interactions may manifest themselves as functional antagonisms; binding may correlate with enhancement or synergism; the formation of some complexes may yield clues about how drugs may be targeted to specific cell types in vivo and provide leads for the development of antidotes for drug overdoses or poisoning; the binding of one molecule to another may mimic receptor binding; and complexation may provide novel ways of protecting and delivering drugs. Relevant examples from each type of application are reviewed involving peptide-peptide interactions; peptide-aromatic compound interactions; aromatic-aromatic compound interactions; vitamin-aromatic compound interactions; and polycyclic compound interactions. We argue that screening for molecular complementarity of small molecules turns ligands such as neurotransmitters and their metabolites, hormones, and drugs themselves, into direct targets of drug development that can augment screening new compounds for activity against receptors and second messenger systems. We believe that the small molecule complementarity approach is novel, fruitful and under-utilized.

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“…The evolution of host-control compounds was probably guided by molecular complementarity which selects from the diversity of biological molecules those that are able to stabilize and interact functionally with each other (15); hence, candidate host-control compounds produced by bacteria include the macromolecules or fragments of macromolecules (16) that bind to metabolites or that bind to the receptors of those metabolites or even the receptors themselves (such as the bacterial adrenergic receptors [17]). One possible example of molecular complementarity is the major cell wall breakdown product muramyl dipeptide, or "adjuvant peptide," which not only stimulates an inflammatory response via the NOD proteins (18) but also mimics serotonin to cause drowsiness (19,20). Drowsiness may also be caused by the administration of another bacterial product, flagellin, which acts via a Toll-like receptor, TLR5 (A. Gewirtz, unpublished data).…”

Section: Evidencementioning

confidence: 99%

Hypothesis: Bacteria Control Host Appetites

Norris¹,

Molina²,

Gewirtz³

2012

Journal of Bacteriology

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cTo help investigate the relationship between inflammatory and other diseases and the composition of the gut microbiota, we propose that a positive-feedback loop exists between the preferences of the host for a particular dietary regimen, the composition of the gut microbiota that depends on this regimen, and the preferences of the host as influenced by the gut microbiota. We cite evidence in support of this hypothesis and make testable predictions.

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‘Molecular sandwiches’ as a basis for structural and functional similarities of interferons, MSH, ACTH, LHRH, myelin basic protein, and albumins

Cited by 13 publications

References 35 publications

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Peptide self-aggregation and peptide complementarity as bases for the evolution of peptide receptors: a review

Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies

Hypothesis: Bacteria Control Host Appetites

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