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Structure and dynamics of Candida rugosa lipase: the role of organic solvent

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Abstract

The effect of organic solvent on the structure and dynamics of proteins was investigated by multiple molecular dynamics simulations (1 ns each) of Candida rugosa lipase in water and in carbon tetrachloride. The choice of solvent had only a minor structural effect. For both solvents the open and the closed conformation of the lipase were near to their experimental X-ray structures (Cα rms deviation 1–1.3 Å). However, the solvents had a highly specific effect on the flexibility of solvent-exposed side chains: polar side chains were more flexible in water, but less flexible in organic solvent. In contrast, hydrophobic residues were more flexible in organic solvent, but less flexible in water. As a major effect solvent changed the dynamics of the lid, a mobile element involved in activation of the lipase, which fluctuated as a rigid body about its average position. While in water the deviations were about 1.6 Å, organic solvent reduced flexibility to 0.9 Å. This increase rigidity was caused by two salt bridges (Lys85–Asp284, Lys75–Asp79) and a stable hydrogen bond (Lys75–Asn 292) in organic solvent. Thus, organic solvents stabilize the lid but render the side chains in the hydrophobic substrate-binding site more mobile.

Figure Superimposition of open (black, PDB entry 1CRL) and closed (gray, PDB entry 1TRH) conformers of C. rugosa lipase. The mobile lid is indicated

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Abbreviations

CALB:

Candida antarctica lipase B

CRL:

Candida rugosa lipase

CCl4 :

carbon tetrachloride

MD:

molecular dynamics

PCL:

Pseudomonas cepacia lipase

Rmsd:

root-mean square deviation(s)

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Acknowledgements

This work was supported by the German Federal Ministry of Education and Research (project WTZ-MYS 02/001) and Malaysian Ministry of Science, Technology and Environment (project IRPA 09-02-04-001/BTK/TD/004).

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Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Bimo Ario Tejo & Abu Bakar Salleh

  2. Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Abu Bakar Salleh

  3. Institute of Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany

    Juergen Pleiss

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  1. Bimo Ario Tejo
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  2. Abu Bakar Salleh
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Correspondence to Juergen Pleiss.

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Tejo, B.A., Salleh, A.B. & Pleiss, J. Structure and dynamics of Candida rugosa lipase: the role of organic solvent. J Mol Model 10, 358–366 (2004). https://doi.org/10.1007/s00894-004-0203-z

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