Communication between the nucleotide site and the main molecular hinge of 3-phosphoglycerate kinase

Judit Szabó, A. Varga, Beáta Flachner, Peter V. Konarev, Dmitri I. Svergun, P. Závodszky, M. Vas

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

3-Phosphoglycerate kinase is a hinge-bending enzyme with substrate-assisted domain closure. However, the closure mechanism has not been described in terms of structural details. Here we present experimental evidence of the participation of individual substrate binding side chains in the operation of the main hinge which is distant from the substrate binding sites. The combined mutational, kinetic, and structural (DSC and SAXS) data for human 3-phosphoglycerate kinase have shown that catalytic residue R38, which also binds the substrate 3-phosphoglycerate, is essential in inducing domain closure. Similarly, residues K219, N336, and E343 which interact with the nucleotide substrates are involved in the process of domain closure. The other catalytic residue, K215, covers a large distance during catalysis but has no direct role in domain closure. The transmission path of the nucleotide effect toward the main hinge of PGK is described for the first time at the level of interactions existing in the tertiary structure.

Original languageEnglish
Pages (from-to)6735-6744
Number of pages10
JournalBiochemistry
Volume47
Issue number26
DOIs
Publication statusPublished - Jul 1 2008

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Phosphoglycerate Kinase
Hinges
Nucleotides
Communication
Substrates
Catalysis
Binding Sites
Enzymes
3-phosphoglycerate
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Communication between the nucleotide site and the main molecular hinge of 3-phosphoglycerate kinase. / Szabó, Judit; Varga, A.; Flachner, Beáta; Konarev, Peter V.; Svergun, Dmitri I.; Závodszky, P.; Vas, M.

In: Biochemistry, Vol. 47, No. 26, 01.07.2008, p. 6735-6744.

Research output: Contribution to journalArticle

Szabó, Judit ; Varga, A. ; Flachner, Beáta ; Konarev, Peter V. ; Svergun, Dmitri I. ; Závodszky, P. ; Vas, M. / Communication between the nucleotide site and the main molecular hinge of 3-phosphoglycerate kinase. In: Biochemistry. 2008 ; Vol. 47, No. 26. pp. 6735-6744.
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