Atomic structure of thymidylate synthase: Target for rational drug design

Larry W. Hardy, Janet S. Finer-Moore, William "Bill" Montfort, Melvin O. Jones, Daniel V. Santi, Robert M. Stroud

Research output: Contribution to journalArticle

284 Citations (Scopus)

Abstract

The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five-stranded β sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding.

Original languageEnglish (US)
Pages (from-to)448-455
Number of pages8
JournalScience
Volume235
Issue number4787
StatePublished - 1987
Externally publishedYes

Fingerprint

Lactobacillus casei
Thymidylate Synthase
Drug Design
Arginine
Catalytic Domain
Phosphates
Amino Acids
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Hardy, L. W., Finer-Moore, J. S., Montfort, W. B., Jones, M. O., Santi, D. V., & Stroud, R. M. (1987). Atomic structure of thymidylate synthase: Target for rational drug design. Science, 235(4787), 448-455.

Atomic structure of thymidylate synthase : Target for rational drug design. / Hardy, Larry W.; Finer-Moore, Janet S.; Montfort, William "Bill"; Jones, Melvin O.; Santi, Daniel V.; Stroud, Robert M.

In: Science, Vol. 235, No. 4787, 1987, p. 448-455.

Research output: Contribution to journalArticle

Hardy, LW, Finer-Moore, JS, Montfort, WB, Jones, MO, Santi, DV & Stroud, RM 1987, 'Atomic structure of thymidylate synthase: Target for rational drug design', Science, vol. 235, no. 4787, pp. 448-455.
Hardy LW, Finer-Moore JS, Montfort WB, Jones MO, Santi DV, Stroud RM. Atomic structure of thymidylate synthase: Target for rational drug design. Science. 1987;235(4787):448-455.
Hardy, Larry W. ; Finer-Moore, Janet S. ; Montfort, William "Bill" ; Jones, Melvin O. ; Santi, Daniel V. ; Stroud, Robert M. / Atomic structure of thymidylate synthase : Target for rational drug design. In: Science. 1987 ; Vol. 235, No. 4787. pp. 448-455.
@article{a86a50e2020345e69d82a1833a21451a,
title = "Atomic structure of thymidylate synthase: Target for rational drug design",
abstract = "The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five-stranded β sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding.",
author = "Hardy, {Larry W.} and Finer-Moore, {Janet S.} and Montfort, {William {"}Bill{"}} and Jones, {Melvin O.} and Santi, {Daniel V.} and Stroud, {Robert M.}",
year = "1987",
language = "English (US)",
volume = "235",
pages = "448--455",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "4787",

}

TY - JOUR

T1 - Atomic structure of thymidylate synthase

T2 - Target for rational drug design

AU - Hardy, Larry W.

AU - Finer-Moore, Janet S.

AU - Montfort, William "Bill"

AU - Jones, Melvin O.

AU - Santi, Daniel V.

AU - Stroud, Robert M.

PY - 1987

Y1 - 1987

N2 - The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five-stranded β sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding.

AB - The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five-stranded β sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding.

UR - http://www.scopus.com/inward/record.url?scp=0023121146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023121146&partnerID=8YFLogxK

M3 - Article

C2 - 3099389

AN - SCOPUS:0023121146

VL - 235

SP - 448

EP - 455

JO - Science

JF - Science

SN - 0036-8075

IS - 4787

ER -