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The mechanism of aconitase: 1.8 Å resolution crystal structure of the S642A:citrate complex

Published online by Cambridge University Press:  01 December 1999

S.J. LLOYD
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
H. LAUBLE
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 Present address: Max Delbruck Centrum für Molekuläre Medizin, Robert Roessle Strasse 10, 13125 Berlin, Germany.
G.S. PRASAD
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
C.D. STOUT
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
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Abstract

The crystal structure of the S642A mutant of mitochondrial aconitase (mAc) with citrate bound has been determined at 1.8 Å resolution and 100 K to capture this binding mode of substrates to the native enzyme. The 2.0 Å resolution, 100 K crystal structure of the S642A mutant with isocitrate binding provides a control, showing that the Ser → Ala replacement does not alter the binding of substrates in the active site. The aconitase mechanism requires that the intermediate product, cis-aconitate, flip over by 180° about the Cα–Cβ double bond. Only one of these two alternative modes of binding, that of the isocitrate mode, has been previously visualized. Now, however, the structure revealing the citrate mode of binding provides direct support for the proposed enzyme mechanism.

Type
Research Article
Copyright
© 1999 The Protein Society

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