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Dynamical Aspects of TEM-1 βbeta-Lactamase Probed by Molecular Dynamics
Danilo Roccatano1, 4, Gianluca Sbardella2,
Massimiliano Aschi1, Gianfranco Amicosante3,
Cecilia Bossa2, Alfredo Di Nola2
and Fernando Mazza1
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Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universit degli Studi, V. Vetoio, 67010 L’Aquila, Italy |
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Dipartimento di Chimica, Universit degli Studi “La Sapienza”, P.le A. Moro 5, 00185 Rome, Italy |
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Dipartimento di Scienze e Tecnologie Biomediche, Universit degli Studi, V. Vetoio, 67010 L’Aquila, Italy |
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School of Engineering and Science, International University Bremen, Campus Ring, 1D-28725 Bremen, Germany |
Received: 02 February 2005 Accepted: 09 May 2005
Abstract:
The dynamical aspects of the fully hydrated TEM-1 βbeta-lactamase have been determined by a 5 ns Molecular Dynamics simulation. Starting from the crystallographic coordinates, the protein shows a relaxation in water with an overall root mean square deviation from the crystal structure increasing up to 0.17 nm, within the first nanosecond. Then a plateau is reached and the molecule fluctuates around an equilibrium conformation. The results obtained in the first nanosecond are in agreement with those of a previous simulation (Diaz et al., J. Am. Chem. Soc., (2003) 125, 672–684). The successive equilibrium conformation in solution shows an increased mobility characterized by the following aspects. A flap-like translational motion anchores the Ω-loop to the body of the enzyme. A relevant part of the backbone dynamics implies a rotational motion of one domain relative to the other. The water molecules in the active site can exchange with different residence times. The H-bonding networks formed by the catalytic residues are frequently interrupted by water molecules that could favour proton transfer reactions. An additional simulation, where the aspartyl dyad D214–D233 was considered fully deprotonated, shows that the active site is destabilized.
Keywords domain motion - H-bonding networks - Molecular Dynamics - Ω-loop - TEM-1 β-lactamase - water bridges
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Fernando Mazza |