Protein folding and function: the N-terminal fragment in adenylate kinase

Biophysical Journal
S KumarRuth Nussinov

Abstract

Three-dimensional protein folds range from simple to highly complex architectures. In complex folds, some building block fragments are more important for correct protein folding than others. Such fragments are typically buried in the protein core and mediate interactions between other fragments. Here we present an automated, surface area-based algorithm that is able to indicate which, among all local elements of the structure, is critical for the formation of the native fold, and apply it to structurally well-characterized proteins. In particular, we focus on adenylate kinase. The fragment containing the phosphate binding, P-loop (the "giant anion hole") flanked by a beta-strand and an alpha-helix near the N-terminus, is identified as a critical building block. This building block shows a high degree of sequence and structural conservation in all adenylate kinases. The results of our molecular dynamics simulations are consistent with this identification. In its absence, the protein flips to a stable, non-native state. In this misfolded conformation, the other local elements of the structure are in their native-like conformations; however, their association is non-native. Furthermore, this element is critically important for the...Continue Reading

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Citations

May 3, 2002·European Journal of Biochemistry·Eleonora CerasoliNicholas C Price
Jun 19, 2002·Protein Science : a Publication of the Protein Society·Chung-Jung TsaiRuth Nussinov
Jun 30, 2009·Photochemistry and Photobiology·Farangis AtaeiKhosro Khajeh
Feb 3, 2005·Proteins·Han-Kuen LiangJenn-Kang Hwang
Jul 29, 2004·Proteins·Adi BarzilaiRuth Nussinov
May 23, 2003·Protein Science : a Publication of the Protein Society·Nurit HaspelRuth Nussinov
Sep 22, 2009·The International Journal of Biochemistry & Cell Biology·Christakis PanayiotouAnna Karlsson
Apr 5, 2002·Proteins·Themis LazaridisFrancois Gandolfo
Jul 2, 2003·Proteins·Themis Lazaridis
Jan 16, 2002·Journal of Biomolecular Structure & Dynamics·N SinhaR Nussinov
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Aug 14, 2009·The Journal of Physical Chemistry. B·Yury E ShapiroEva Meirovitch
Jul 14, 2010·Progress in Nuclear Magnetic Resonance Spectroscopy·Eva MeirovitchJack H Freed
Nov 9, 2004·Proteins·Chen-Hsiung ChanJenn-Kang Hwang
Mar 23, 2019·The Journal of Physical Chemistry. B·Fernando Bergasa-CaceresHerschel A Rabitz
Jun 28, 2006·The Journal of Physical Chemistry. B·Hongfeng Lou, Robert I Cukier

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