Plastic adaptation toward mutations in proteins: Structural comparison of thymidylate synthases

K. M. Perry, E. B. Fauman, J. S. Finer-Moore, William "Bill" Montfort, G. F. Maley, F. Maley, R. M. Stroud

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

The structure of thymidylate synthase (TS) from Escherichia coli was solved from cubic crystals with a = 133 Å grown under reducing conditions at pH 7.0, and refined to R = 22% at 2.1 Å resolution. The structure is compared with that from Lactobacillus casei solved to R = 21% at 2.3 Å resolution. The structures are compared using a difference distance matrix, which identifies a common core of residues that retains the same relationship to one another in both species. After subtraction of the effects of a 50 amino acid insert present in Lactobacillus casei, differences in position of atoms correlate with temperature factors and with distance from the nearest substituted residue. The dependence of structural difference on thermal factor is parameterized and reflects both errors in coordinates that correlate with thermal factor, and the increased width of the energy well in which atoms of high thermal factor lie. The dependence of structural difference on distance from the nearest substitution also depends on thermal factors and shows an exponential dependence with half maximal effect at 3.0 Å from the substitution. This represents the plastic accommodation of the protein which is parameterized in terms of thermal B factor and distance from a mutational change.

Original languageEnglish (US)
Pages (from-to)315-333
Number of pages19
JournalProteins: Structure, Function and Genetics
Volume8
Issue number4
DOIs
StatePublished - 1990

Fingerprint

Thymidylate Synthase
Plastics
Hot Temperature
Mutation
Lactobacillus casei
Proteins
Substitution reactions
Atoms
Escherichia coli
Amino Acids
Crystals
Temperature

Keywords

  • B factor
  • crystal structure
  • mutation
  • plasticity
  • thymidylate synthase

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

Plastic adaptation toward mutations in proteins : Structural comparison of thymidylate synthases. / Perry, K. M.; Fauman, E. B.; Finer-Moore, J. S.; Montfort, William "Bill"; Maley, G. F.; Maley, F.; Stroud, R. M.

In: Proteins: Structure, Function and Genetics, Vol. 8, No. 4, 1990, p. 315-333.

Research output: Contribution to journalArticle

Perry, K. M. ; Fauman, E. B. ; Finer-Moore, J. S. ; Montfort, William "Bill" ; Maley, G. F. ; Maley, F. ; Stroud, R. M. / Plastic adaptation toward mutations in proteins : Structural comparison of thymidylate synthases. In: Proteins: Structure, Function and Genetics. 1990 ; Vol. 8, No. 4. pp. 315-333.
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