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1zdp
From Proteopedia
(New page: 200px<br /><applet load="1zdp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zdp, resolution 1.70Å" /> '''Crystal Structure An...) |
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| - | [[Image:1zdp.gif|left|200px]]<br /><applet load="1zdp" size=" | + | [[Image:1zdp.gif|left|200px]]<br /><applet load="1zdp" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zdp, resolution 1.70Å" /> | caption="1zdp, resolution 1.70Å" /> | ||
'''Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan'''<br /> | '''Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan | + | The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan bound to thermolysin have been determined crystallographically and refined to residuals of 0.183 and 0.187 at 1.7-A resolution. Thiorphan [N-[(S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]glycine] [HSCH2CH(CH2C6H5)CONHC-H2COOH] and retro-thiorphan [[[(R)-1-(mercaptomethyl)-2-phenylethyl] amino]-3-oxopropanoic acid] [HSCH2CH(CH2C6H5)NHCOCH2COOH] are isomeric thiol-containing inhibitors of endopeptidase EC 24-11 (also called "enkephalinase"). The mode of binding of thiorphan to thermolysin is similar to that of (2-benzyl-3-mercaptopropanoyl)-L-alanylglycinamide [Monzingo, A.F., & Matthews, B.W. (1982) Biochemistry 21, 3390-3394] with the inhibitor sulfur atom coordinated to the active site zinc and the peptide portion forming substrate-like interactions with the enzyme. The isomeric inhibitor retro-thiorphan, which differs from thiorphan by the inversion of an amide bond, utilizes very similar interactions with enzyme. Despite the inversion of the -CO-NH- linkage the carbonyl oxygen and amide nitrogen display very similar hydrogen bonding, as anticipated by B.P. Roques et al. [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3178-3182]. These results explain why thermolysin and possibly other zinc endopeptidases such as endopeptidase EC 24-11 fail to discriminate between these retro-inverso inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZDP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus] with CA, ZN and TIO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] Full crystallographic information is available from [http:// | + | 1ZDP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=TIO:'>TIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thermolysin Thermolysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.27 3.4.24.27] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermolysin]] | [[Category: Thermolysin]] | ||
| - | [[Category: Fournie-Zaluski, M | + | [[Category: Fournie-Zaluski, M C.]] |
| - | [[Category: Matthews, B | + | [[Category: Matthews, B W.]] |
| - | [[Category: Roderick, S | + | [[Category: Roderick, S L.]] |
| - | [[Category: Roques, B | + | [[Category: Roques, B P.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: TIO]] | [[Category: TIO]] | ||
| Line 23: | Line 23: | ||
[[Category: enzyme-inhibitor complex; zinc endopeptidase; gamma turn; thermostable]] | [[Category: enzyme-inhibitor complex; zinc endopeptidase; gamma turn; thermostable]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:38 2008'' |
Revision as of 14:14, 21 February 2008
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Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan
Overview
The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan bound to thermolysin have been determined crystallographically and refined to residuals of 0.183 and 0.187 at 1.7-A resolution. Thiorphan [N-[(S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]glycine] [HSCH2CH(CH2C6H5)CONHC-H2COOH] and retro-thiorphan [[[(R)-1-(mercaptomethyl)-2-phenylethyl] amino]-3-oxopropanoic acid] [HSCH2CH(CH2C6H5)NHCOCH2COOH] are isomeric thiol-containing inhibitors of endopeptidase EC 24-11 (also called "enkephalinase"). The mode of binding of thiorphan to thermolysin is similar to that of (2-benzyl-3-mercaptopropanoyl)-L-alanylglycinamide [Monzingo, A.F., & Matthews, B.W. (1982) Biochemistry 21, 3390-3394] with the inhibitor sulfur atom coordinated to the active site zinc and the peptide portion forming substrate-like interactions with the enzyme. The isomeric inhibitor retro-thiorphan, which differs from thiorphan by the inversion of an amide bond, utilizes very similar interactions with enzyme. Despite the inversion of the -CO-NH- linkage the carbonyl oxygen and amide nitrogen display very similar hydrogen bonding, as anticipated by B.P. Roques et al. [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3178-3182]. These results explain why thermolysin and possibly other zinc endopeptidases such as endopeptidase EC 24-11 fail to discriminate between these retro-inverso inhibitors.
About this Structure
1ZDP is a Single protein structure of sequence from Bacillus thermoproteolyticus with , and as ligands. Active as Thermolysin, with EC number 3.4.24.27 Full crystallographic information is available from OCA.
Reference
Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin., Roderick SL, Fournie-Zaluski MC, Roques BP, Matthews BW, Biochemistry. 1989 Feb 21;28(4):1493-7. PMID:2719912
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