PDBsum entry 4b2c

Hydrolase/hydrolase inhibitor

PDB id: 4b2c

Contents

Protein chains

223 a.a.

71 a.a.

Ligands

GOL ×20

EDO ×4

Metals

_CA ×2

_CL ×2

Waters ×505

PDB id:

4b2c

Name:

Hydrolase/hydrolase inhibitor

Title:

Structure of the factor xa-like trypsin variant triple-ala (tpa) in complex with eglin c

Structure:

Cationic trypsin. Chain: a, c. Synonym: beta-trypsin, alpha-trypsin chain 1, alpha-trypsin chain 2. Engineered: yes. Mutation: yes. Eglin c. Chain: b, d. Engineered: yes. Mutation: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Expressed in: escherichia coli. Expression_system_taxid: 562. Hirudo medicinalis. Medicinal leech. Organism_taxid: 6421. Expression_system_taxid: 562

Resolution:

1.43Å R-factor: 0.158 R-free: 0.182

Authors:

A.Menzel,P.Neumann,M.T.Stubbs

Key ref:

A.Menzel et al. (2014). Thermodynamic signatures in macromolecular interactions involving conformational flexibility. Biol Chem, 395, 905-911. PubMed id: 25003391 DOI: 10.1515/hsz-2014-0177

Date:

13-Jul-12 Release date: 01-Aug-12

Protein chains

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.*

Protein chains

P01051  (ICIC_HIRME) -  Eglin C from Hirudo medicinalis

Seq: 70 a.a.

Struc: 71 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

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

DOI no: 10.1515/hsz-2014-0177

Biol Chem 395:905-911 (2014)

PubMed id: 25003391

Thermodynamic signatures in macromolecular interactions involving conformational flexibility.

A.Menzel, P.Neumann, C.Schwieger, M.T.Stubbs.

ABSTRACT

Abstract The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities.