1z9g: Difference between revisions
New page: left|200px<br /><applet load="1z9g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z9g, resolution 1.70Å" /> '''Crystal Structure An... |
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[[Image:1z9g.gif|left|200px]]<br /><applet load="1z9g" size=" | [[Image:1z9g.gif|left|200px]]<br /><applet load="1z9g" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1z9g, resolution 1.70Å" /> | caption="1z9g, resolution 1.70Å" /> | ||
'''Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (R)-retro-thiorphan'''<br /> | '''Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (R)-retro-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== | ||
1Z9G 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 RRT 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:// | 1Z9G 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=RRT:'>RRT</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=1Z9G 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: RRT]] | [[Category: RRT]] | ||
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[[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 16:13:24 2008'' | ||
Revision as of 14:13, 21 February 2008
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Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (R)-retro-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
1Z9G is a Single protein structure of sequence from Bacillus thermoproteolyticus with CA, ZN and RRT 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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