2NW6

Burkholderia cepacia lipase complexed with S-inhibitor

Summary for 2NW6

• Entry DOI: 10.2210/pdb2nw6/pdb
• Related: 1HQD 1OIL 2LIP 3LIP 4LIP 5LIP
• Descriptor: Lipase, CALCIUM ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: pseudomonas cepacia lipase, racemic sec alcohols, transition state (ts) analogue, molecular modelling, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Burkholderia cepacia
• Total number of polymer chains: 1
• Total formula weight: 33476.50

Authors

Luic, M.,Stefanic, Z. (deposition date: 2006-11-14, release date: 2007-12-04, Last modification date: 2024-10-09)

Primary citation

Luic, M.,Stefanic, Z.,Ceilinger, I.,Hodoscek, M.,Janezic, D.,Lenac, T.,Asler, I.L.,Sepac, D.,Tomic, S.
Combined X-ray diffraction and QM/MM study of the Burkholderia cepacia lipase-catalyzed secondary alcohol esterification
J.Phys.Chem.B, 112:4876-4883, 2008

PubMed Abstract: To understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) toward secondary alcohol, (R,S)-1-phenoxy-2-hydroxybutane (1), and its ester (E1), we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC, and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed. To check the possibility of chemical transformation, four different orientations of the substrate (two for each enantiomer) were chosen, and a series of ab initio QM/MM calculations were accomplished. Starting from the covalent complex, we modeled the ester (E1) hydrolysis and the alcohol (1) esterification. The calculations revealed that ester release is possible starting with all four covalent complexes. Alcohol release from the BCL-E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. These results show that the crystallographically determined binding modes should be taken with caution when modeling chemical reactions.

PubMed: 18386861
DOI: 10.1021/jp077717u

Experimental method

X-RAY DIFFRACTION (1.8 Å)