2gzf

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==Overview==
==Overview==
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The crystal structure of the cytotoxic endonuclease domain from the, bacterial toxin colicin E9 in complex with its cognate immunity protein, Im9 reveals that the inhibitor does not bind at the active site, the core, of which comprises the HNH motif found in intron-encoded homing, endonucleases, but rather at an adjacent position leaving the active site, exposed yet unable to bind DNA because of steric and electrostatic clashes, with incoming substrate. Although its mode of action is unorthodox, Im9 is, a remarkably effective inhibitor since it folds within milliseconds and, then associates with its target endonuclease at the rate of diffusion to, form an inactive complex with sub-femtomolar binding affinity. This, hyperefficient mechanism of inhibition could be well suited to other toxic, enzyme systems, particularly where the substrate is a polymer extending, beyond the boundaries of the active site.
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The crystal structure of the cytotoxic endonuclease domain from the bacterial toxin colicin E9 in complex with its cognate immunity protein Im9 reveals that the inhibitor does not bind at the active site, the core of which comprises the HNH motif found in intron-encoded homing endonucleases, but rather at an adjacent position leaving the active site exposed yet unable to bind DNA because of steric and electrostatic clashes with incoming substrate. Although its mode of action is unorthodox, Im9 is a remarkably effective inhibitor since it folds within milliseconds and then associates with its target endonuclease at the rate of diffusion to form an inactive complex with sub-femtomolar binding affinity. This hyperefficient mechanism of inhibition could be well suited to other toxic enzyme systems, particularly where the substrate is a polymer extending beyond the boundaries of the active site.
==About this Structure==
==About this Structure==
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Hemmings, A.M.]]
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[[Category: Hemmings, A M.]]
[[Category: Kleanthous, C.]]
[[Category: Kleanthous, C.]]
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[[Category: Kolade, O.O.]]
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[[Category: Kolade, O O.]]
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[[Category: Kuhlmann, U.C.]]
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[[Category: Kuhlmann, U C.]]
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[[Category: Santi, P.S.]]
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[[Category: Santi, P S.]]
[[Category: PO4]]
[[Category: PO4]]
[[Category: ZN]]
[[Category: ZN]]
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[[Category: protein-protein complex]]
[[Category: protein-protein complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:39:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:36:41 2008''

Revision as of 15:36, 21 February 2008


2gzf, resolution 1.750Å

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Crystal structure of the E9 DNase domain with a mutant immunity protein IM9 (Y54F)

Overview

The crystal structure of the cytotoxic endonuclease domain from the bacterial toxin colicin E9 in complex with its cognate immunity protein Im9 reveals that the inhibitor does not bind at the active site, the core of which comprises the HNH motif found in intron-encoded homing endonucleases, but rather at an adjacent position leaving the active site exposed yet unable to bind DNA because of steric and electrostatic clashes with incoming substrate. Although its mode of action is unorthodox, Im9 is a remarkably effective inhibitor since it folds within milliseconds and then associates with its target endonuclease at the rate of diffusion to form an inactive complex with sub-femtomolar binding affinity. This hyperefficient mechanism of inhibition could be well suited to other toxic enzyme systems, particularly where the substrate is a polymer extending beyond the boundaries of the active site.

About this Structure

2GZF is a Protein complex structure of sequences from Escherichia coli with and as ligands. Active as Deoxyribonuclease I, with EC number 3.1.21.1 Full crystallographic information is available from OCA.

Reference

Structural and mechanistic basis of immunity toward endonuclease colicins., Kleanthous C, Kuhlmann UC, Pommer AJ, Ferguson N, Radford SE, Moore GR, James R, Hemmings AM, Nat Struct Biol. 1999 Mar;6(3):243-52. PMID:10074943

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