Refined 1.2 Å crystal structure of the complex formed between subtilisin Carlsberg and the inhibitor eglin c
Structural biology article published in EMBO Journal (1986)
Abstract
The crystal structure of the complex formed between eglin c, an elastase inhibitor from the medical leech, and subtilisin Carlsberg has been determined at 1.2 A resolution by a combination of Patterson search methods and isomorphous replacement techniques. The structure has been refined to a crystallographic R-value of 0.18 (8-1.2 A). Eglin consists of a four-stranded beta-sheet with an alpha-helical segment and the protease-binding loop fixed on opposite sides. This loop, which contains the reactive site Leu45I--Asp46I, is mainly held in its conformation by unique electrostatic/hydrogen bond interactions of Thr44I and Asp46I with the side chains of Arg53I and Arg51I which protrude from the hydrophobic core of the molecule. The conformation around the reactive site is similar to that found in other proteinase inhibitors. The nine residues of the binding loop Gly40I--Arg48I are involved in direct contacts with subtilisin. In this interaction, eglin segment Pro42I--Thr44I forms a three-stranded anti-parallel beta-sheet with subtilisin segments Gly100--Gly102 and Ser125--Gly127. The reactive site peptide bond of eglin is intact, and Ser221 OG of the enzyme is 2.81 A apart from the carbonyl carbon.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
1.2 Å crystal structure of the subtilisin Carlsberg-eglin C complex shows leech eglin C as a four-stranded β-sheet with α-helix and protease-binding loop forming a three-stranded antiparallel β-sheet with subtilisin.
Why This Matters for Hirudotherapy
This study determined the refined 1.2 Å resolution X-ray crystal structure of the complex between eglin c—an elastase inhibitor from the medicinal leech—and subtilisin Carlsberg, using Patterson search and isomorphous replacement methods (R-value 0.18). The structure shows eglin c as a four-stranded beta-sheet with an alpha-helical segment and a protease-binding loop (reactive site Leu45I-Asp46I) held by electrostatic/hydrogen-bond interactions, with nine loop residues contacting subtilisin to form a three-stranded anti-parallel beta-sheet; the reactive-site peptide bond remains intact. This is relevant to ASH's domain as high-resolution structural characterization of a leech-secretome protease inhibitor. Caveat: this is purely structural (X-ray crystallography) and offers no therapeutic, in-vivo, or hirudotherapy data.
Citation
Refined 1.2 Å crystal structure of the complex formed between subtilisin Carlsberg and the inhibitor eglin c.
Bode W, Papamokos E, Musil D, Seemueller U, Fritz H · The EMBO journal, 1986
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