Document Detail


Molecular recognition by secondary metabolites.
MedLine Citation:
PMID:  2372307     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aspects of molecular recognition based on the interaction between the vancomycin group of antibiotics and bacterial cell wall precursor analogues are discussed. The energetically unfavourable folding-in of the residue 1 sidechain in vancomycin and ristocetin A is discussed in terms of the favourable entropy associated with simultaneous release of solvent molecules. The effect of the sugar amino substituent on the strength of an adjacent hydrophobic interaction in the vancomycin/acetyl-D-Ala-D-Ala complex is rationalised as an intramolecular "salting-out" of hydrocarbon entities. The slow on-rate for dimerisation of the ristocetin A/N,N-diacetyl-L-Lys-D-Ala-D-Ala complex is attributed to the need for the relatively rigid peptide backbone of the antibiotic to be extensively desolvated before dimerisation can occur. Some of these concepts are then applied to understanding the interactions between antibiotics and the minor groove of double-helical DNA, the receptor site with which they have probably evolved to interact. Two structural motifs (pi-polarised aromatic rings and deoxy sugars) are postulated to be important in this recognition process. The possible roles of these structural features are discussed.
Authors:
D H Williams; M J Stone; R J Mortishire-Smith; P R Hauck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  40     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1990-08-21     Completed Date:  1990-08-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  27-34     Citation Subset:  IM    
Affiliation:
University Chemical Laboratory, Cambridge, U.K.
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MeSH Terms
Descriptor/Qualifier:
Aminoglycosides
Anti-Bacterial Agents / metabolism*
Base Sequence
Binding Sites
DNA / metabolism*
Membrane Proteins / metabolism
Molecular Sequence Data
Peptides
Protein Conformation
Ristocetin / metabolism
Structure-Activity Relationship
Vancomycin / metabolism
Chemical
Reg. No./Substance:
0/Aminoglycosides; 0/Anti-Bacterial Agents; 0/Membrane Proteins; 0/Peptides; 11021-66-2/ristocetin A; 1404-55-3/Ristocetin; 1404-90-6/Vancomycin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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