PDBsum entry 1ce5

Hydrolase

PDB id: 1ce5

Contents

Protein chain

223 a.a. *

Ligands

SO4

BEN

Metals

_CA

_CL

Waters ×127

* Residue conservation analysis

PDB id:

1ce5

Name:

Hydrolase

Title:

Bovine pancreas beta-trypsin in complex with benzamidine

Structure:

Protein (trypsin). Chain: a. Ec: 3.4.21.4

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Other_details: bovine pancreas beta-trypsin purchased from worthington biochemical corporation

Resolution:

1.90Å R-factor: 0.161 R-free: 0.186

Authors:

N.Ota,C.Stroupe,J.M.S.Ferreira-Da-Silva,S.S.Shah,M.Mares-Guia, A.T.Brunger

Key ref:

N.Ota et al. (1999). Non-Boltzmann thermodynamic integration (NBTI) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine. Proteins, 37, 641-653. PubMed id: 10651279 DOI: 10.1002/(SICI)1097-0134(19991201)37:4<641::AID-PROT14>3.0.CO;2-W

Date:

16-Mar-99 Release date: 23-Mar-99

Protein chain

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

DOI no: 10.1002/(SICI)1097-0134(19991201)37:4<641::AID-PROT14>3.0.CO;2-W

Proteins 37:641-653 (1999)

PubMed id: 10651279

Non-Boltzmann thermodynamic integration (NBTI) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine.

N.Ota, C.Stroupe, J.M.Ferreira-da-Silva, S.A.Shah, M.Mares-Guia, A.T.Brunger.

ABSTRACT

The relative free energies of binding of trypsin to two amine inhibitors, benzamidine (BZD) and benzylamine (BZA), were calculated using non-Boltzmann thermodynamic integration (NBTI). Comparison of the simulations with the crystal structures of both complexes, trypsin-BZD and trypsin-BZA, shows that NBTI simulations better sample conformational space relative to thermodynamic integration (TI) simulations. The relative binding free energy calculated using NBTI was much closer to the experimentally determined value than that obtained using TI. The error in the TI simulation was found to be primarily due to incorrect sampling of BZA's conformation in the binding pocket. In contrast, NBTI produces a smooth mutation from BZD to BZA using a surrogate potential, resulting in a much closer agreement between the inhibitors' conformations and the omit electron density maps. This superior agreement between experiment and simulation, of both relative binding free energy differences and conformational sampling, demonstrates NBTI's usefulness for free energy calculations in macromolecular simulations.

Selected figure(s)

Figure 2.
Figure 2. The change in charges and covalent geometry for the mutation form benzamidine (BZD) to benzylamine (BZA). Dm indicates a dummy atom and C7 of BZD is located at the center of the spherical boundary method.

Figure 4.
Figure 4. Comparison of the binding pocket of crystal structures of trypsin-inhibitor complexes. Superposition of the trypsin-BZA complex (green) onto the trypsin-BZD complex (magenta) using the Ca atoms of trypsin of the reservoir region. The side chain of Gln 192 is not shown because of multiple conformations.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (1999, 37, 641-653) copyright 1999.

Figures were selected by an automated process.