2ar3
From Proteopedia
(New page: 200px<br /><applet load="2ar3" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ar3, resolution 2.20Å" /> '''E90A mutant structur...) |
|||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | We report a structural and functional analysis of the lambda prophage Ba02 | + | We report a structural and functional analysis of the lambda prophage Ba02 endolysin (PlyL) encoded by the Bacillus anthracis genome. We show that PlyL comprises two autonomously folded domains, an N-terminal catalytic domain and a C-terminal cell wall-binding domain. We determined the crystal structure of the catalytic domain; its three-dimensional fold is related to that of the cell wall amidase, T7 lysozyme, and contains a conserved zinc coordination site and other components of the catalytic machinery. We demonstrate that PlyL is an N-acetylmuramoyl-L-alanine amidase that cleaves the cell wall of several Bacillus species when applied exogenously. We show, unexpectedly, that the catalytic domain of PlyL cleaves more efficiently than the full-length protein, except in the case of Bacillus cereus, and using GFP-tagged cell wall-binding domain, we detected strong binding of the cell wall-binding domain to B. cereus but not to other species tested. We further show that a related endolysin (Ply21) from the B. cereus phage, TP21, shows a similar pattern of behavior. To explain these data, and the species specificity of PlyL, we propose that the C-terminal domain inhibits the activity of the catalytic domain through intramolecular interactions that are relieved upon binding of the C-terminal domain to the cell wall. Furthermore, our data show that (when applied exogenously) targeting of the enzyme to the cell wall is not a prerequisite of its lytic activity, which is inherently high. These results may have broad implications for the design of endolysins as therapeutic agents. |
==About this Structure== | ==About this Structure== | ||
| Line 14: | Line 14: | ||
[[Category: N-acetylmuramoyl-L-alanine amidase]] | [[Category: N-acetylmuramoyl-L-alanine amidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
| - | [[Category: Low, L | + | [[Category: Low, L Y.]] |
[[Category: Osterman, A.]] | [[Category: Osterman, A.]] | ||
[[Category: Perego, M.]] | [[Category: Perego, M.]] | ||
| Line 23: | Line 23: | ||
[[Category: endolysin]] | [[Category: endolysin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:30:05 2008'' |
Revision as of 14:30, 21 February 2008
|
E90A mutant structure of PlyL
Overview
We report a structural and functional analysis of the lambda prophage Ba02 endolysin (PlyL) encoded by the Bacillus anthracis genome. We show that PlyL comprises two autonomously folded domains, an N-terminal catalytic domain and a C-terminal cell wall-binding domain. We determined the crystal structure of the catalytic domain; its three-dimensional fold is related to that of the cell wall amidase, T7 lysozyme, and contains a conserved zinc coordination site and other components of the catalytic machinery. We demonstrate that PlyL is an N-acetylmuramoyl-L-alanine amidase that cleaves the cell wall of several Bacillus species when applied exogenously. We show, unexpectedly, that the catalytic domain of PlyL cleaves more efficiently than the full-length protein, except in the case of Bacillus cereus, and using GFP-tagged cell wall-binding domain, we detected strong binding of the cell wall-binding domain to B. cereus but not to other species tested. We further show that a related endolysin (Ply21) from the B. cereus phage, TP21, shows a similar pattern of behavior. To explain these data, and the species specificity of PlyL, we propose that the C-terminal domain inhibits the activity of the catalytic domain through intramolecular interactions that are relieved upon binding of the C-terminal domain to the cell wall. Furthermore, our data show that (when applied exogenously) targeting of the enzyme to the cell wall is not a prerequisite of its lytic activity, which is inherently high. These results may have broad implications for the design of endolysins as therapeutic agents.
About this Structure
2AR3 is a Single protein structure of sequence from Bacillus anthracis with and as ligands. Active as N-acetylmuramoyl-L-alanine amidase, with EC number 3.5.1.28 Full crystallographic information is available from OCA.
Reference
Structure and lytic activity of a Bacillus anthracis prophage endolysin., Low LY, Yang C, Perego M, Osterman A, Liddington RC, J Biol Chem. 2005 Oct 21;280(42):35433-9. Epub 2005 Aug 15. PMID:16103125
Page seeded by OCA on Thu Feb 21 16:30:05 2008
