Access to the carbamate tunnel of carbamoyl phosphate synthetase

Jungwook Kim, Frank M. Raushel

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The X-ray crystal structure of carbamoyl phosphate synthetase (CPS) from Escherichia coli revealed the existence of a molecular tunnel that has been proposed to facilitate the translocation of reaction intermediates between remotely located active sites. Five highly conserved glutamate residues, including Glu-25, Glu-383, Glu-577, Glu-604, and Glu-916, are close together in two clusters in the interior wall of the molecular tunnel that enables the intermediate carbamate to migrate from the site of synthesis to the site of utilization. Two arginines, Arg-306 and Arg-848, are located at either end of the carbamate tunnel and participate in the binding of ATP at each of the two active sites within the large subunit of CPS. The mutation of Glu-25 or Glu-577 results in a diminution in the overall rate of carbamoyl phosphate formation. Similar effects are observed upon mutation of Arg-306 and Arg-848 to alanine residues. The conserved glutamate and arginine residues may function in concert with one another to control entry of carbamate into the tunnel prior to phosphorylation to carbamoyl phosphate. The electrostatic environment of tunnel interior may help to stabilize the tunnel architecture and prevent decomposition of carbamate through protonation.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume425
Issue number1
DOIs
StatePublished - May 1 2004
Externally publishedYes

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Carbamyl Phosphate
Carbamates
Ligases
Tunnels
arginine glutamate
Catalytic Domain
Mutation
Static Electricity
Alanine
Arginine
Glutamic Acid
Reaction intermediates
Phosphorylation
Adenosine Triphosphate
Protonation
X-Rays
Escherichia coli
Electrostatics
Crystal structure
Decomposition

Keywords

  • Carbamate tunnel
  • Carbamoyl phosphate synthetase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Access to the carbamate tunnel of carbamoyl phosphate synthetase. / Kim, Jungwook; Raushel, Frank M.

In: Archives of Biochemistry and Biophysics, Vol. 425, No. 1, 01.05.2004, p. 33-41.

Research output: Contribution to journalArticle

Kim, Jungwook ; Raushel, Frank M. / Access to the carbamate tunnel of carbamoyl phosphate synthetase. In: Archives of Biochemistry and Biophysics. 2004 ; Vol. 425, No. 1. pp. 33-41.
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