PDBsum entry 1slx

Complex (serine protease/inhibitor)

PDB id: 1slx

Contents

Protein chains

131 a.a. *

219 a.a. *

Ligands

ACT

Metals

_ZN

_CA

Waters ×63

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: X-Ray structures of a designed binding site in trypsin show metal-Dependent geometry.
• Authors: L.S.Brinen, W.S.Willett, C.S.Craik, R.J.Fletterick.
• Ref.: Biochemistry, 1996, 35, 5999-6009. [DOI no: 10.1021/bi9530200]
• PubMed id: 8634241

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 94%.

Abstract

The three-dimensional structures of complexes of trypsin N143H, E151H bound to ecotin A86H are determined at 2.0 A resolution via X-ray crystallography in the absence and presence of the transition metals Zn2+, Ni2+, and Cu2+. The binding site for these transition metals was constructed by substitution of key amino acids with histidine at the trypsin-ecotin interface in the S2'/P2' pocket. Three histidine side chains, two on trypsin at positions 143 and 151 and one on ecotin at position 86, anchor the metals and provide extended catalytic recognition for substrates with His in the P2' pocket. Comparisons of the three-dimensional structures show the different geometries that result upon the binding of metal in the engineered tridentate site and suggest a structural basis for the kinetics of the metal-regulated catalysis. Of the three metals, the binding of zinc results in the most favorable binding geometry, not dissimilar to those observed in naturally occurring zinc binding proteins.

Secondary reference #1

• Title: Macromolecular chelation as an improved mechanism of protease inhibition: structure of the ecotin-Trypsin complex.
• Authors: M.E.Mcgrath, T.Erpel, C.Bystroff, R.J.Fletterick.
• Ref.: Embo J, 1994, 13, 1502-1507.
• PubMed id: 8156987