Substrate-induced double sided H-bond network as a means of domain closure in 3-phosphoglycerate kinase

• Published in: FEBS letters Vol. 580; no. 11; pp. 2698 - 2706
• Main Authors: Varga, Andrea, Flachner, Beáta, Konarev, Peter, Gráczer, Éva, Szabó, Judit, Svergun, Dmitri, Závodszky, Péter, Vas, Mária
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.05.2006
• Subjects: 1,3-bisphosphoglycerate; 1,3-BPG; 3-PG; 3-phospho-d-glycerate; 3-phospho-d-glycerate 1-phosphotransferase (EC 2.7.2.3); 3-phospho-d-glycerate kinase; AMP-PCP; AMP-PNP; ATP; Domain movement; Glyceric Acids - chemistry; Glyceric Acids - metabolism; Humans; Hydrogen Bonding; Main hinge; Models, Molecular; PGK; Phosphoglycerate kinase; Phosphoglycerate Kinase - chemistry; Phosphoglycerate Kinase - metabolism; Protein Structure, Tertiary; SAXS; Small-angle X-ray scattering; Substrate effects; Substrate Specificity; β,γ-imido-adenosine-5′-triphosphate; β,γ-methylene-adenosine-5′-triphosphate; AMP-PCP; PGK; 3-PG; Main hinge; Domain movement; Phosphoglycerate kinase; ATP; 1,3-BPG; AMP-PNP; Substrate effects; SAXS; Small-angle X-ray scattering
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.04.024

Closure of the two domains of 3-phosphoglycerate kinase, upon substrate binding, is essential for the enzyme function. The available crystal structures cannot provide sufficient information about the mechanism of substrate assisted domain closure and about the requirement of only one or both substrates, since lattice forces may hinder the large scale domain movements. In this study the known X-ray data, obtained for the open and closed conformations, were probed by solution small-angle X-ray scattering experiments. The results prove that binding of both substrates is essential for domain closure. Molecular graphical analysis, indeed, reveals formation of a double-sided H-bond network, which affects substantially the shape of the main molecular hinge at β-strand L, under the concerted action of both substrates.