1ju3
From Proteopedia
(New page: 200px<br /><applet load="1ju3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ju3, resolution 1.58Å" /> '''BACTERIAL COCAINE ES...) |
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| - | [[Image:1ju3.gif|left|200px]]<br /><applet load="1ju3" size=" | + | [[Image:1ju3.gif|left|200px]]<br /><applet load="1ju3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ju3, resolution 1.58Å" /> | caption="1ju3, resolution 1.58Å" /> | ||
'''BACTERIAL COCAINE ESTERASE COMPLEX WITH TRANSITION STATE ANALOG'''<br /> | '''BACTERIAL COCAINE ESTERASE COMPLEX WITH TRANSITION STATE ANALOG'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Here we report the first structure of a cocaine-degrading enzyme. The | + | Here we report the first structure of a cocaine-degrading enzyme. The bacterial esterase, cocE, hydrolyzes pharmacologically active (-)-cocaine to a non-psychoactive metabolite with a rate faster than any other reported cocaine esterase (kcat = 7.8 s-1 and KM = 640 nM). Because of the high catalytic proficiency of cocE, it is an attractive candidate for novel protein-based therapies for cocaine overdose. The crystal structure of cocE, solved by multiple anomalous dispersion (MAD) methods, reveals that cocE is a serine esterase composed of three domains: (i) a canonical alpha/beta hydrolase fold (ii) an alpha-helical domain that caps the active site and (iii) a jelly-roll-like beta-domain that interacts extensively with the other two domains. The active site was identified within the interface of all three domains by analysis of the crystal structures of transition state analog adduct and product complexes, which were refined at 1.58 A and 1.63 A resolution, respectively. These structural studies suggest that substrate recognition arises partly from interactions between the benzoyl moiety of cocaine and a highly evolved specificity pocket. |
==About this Structure== | ==About this Structure== | ||
| - | 1JU3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp._mb1 Rhodococcus sp. mb1] with PBC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1JU3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp._mb1 Rhodococcus sp. mb1] with <scene name='pdbligand=PBC:'>PBC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JU3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Basran, A.]] | [[Category: Basran, A.]] | ||
| - | [[Category: Bruce, N | + | [[Category: Bruce, N C.]] |
| - | [[Category: Larsen, N | + | [[Category: Larsen, N A.]] |
| - | [[Category: Lerner, R | + | [[Category: Lerner, R A.]] |
| - | [[Category: Rosser, S | + | [[Category: Rosser, S J.]] |
[[Category: Stevens, J.]] | [[Category: Stevens, J.]] | ||
| - | [[Category: Turner, J | + | [[Category: Turner, J M.]] |
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
[[Category: PBC]] | [[Category: PBC]] | ||
[[Category: alpha/beta hydrolase]] | [[Category: alpha/beta hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:26:43 2008'' |
Revision as of 11:26, 21 February 2008
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BACTERIAL COCAINE ESTERASE COMPLEX WITH TRANSITION STATE ANALOG
Overview
Here we report the first structure of a cocaine-degrading enzyme. The bacterial esterase, cocE, hydrolyzes pharmacologically active (-)-cocaine to a non-psychoactive metabolite with a rate faster than any other reported cocaine esterase (kcat = 7.8 s-1 and KM = 640 nM). Because of the high catalytic proficiency of cocE, it is an attractive candidate for novel protein-based therapies for cocaine overdose. The crystal structure of cocE, solved by multiple anomalous dispersion (MAD) methods, reveals that cocE is a serine esterase composed of three domains: (i) a canonical alpha/beta hydrolase fold (ii) an alpha-helical domain that caps the active site and (iii) a jelly-roll-like beta-domain that interacts extensively with the other two domains. The active site was identified within the interface of all three domains by analysis of the crystal structures of transition state analog adduct and product complexes, which were refined at 1.58 A and 1.63 A resolution, respectively. These structural studies suggest that substrate recognition arises partly from interactions between the benzoyl moiety of cocaine and a highly evolved specificity pocket.
About this Structure
1JU3 is a Single protein structure of sequence from Rhodococcus sp. mb1 with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of a bacterial cocaine esterase., Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA, Nat Struct Biol. 2002 Jan;9(1):17-21. PMID:11742345
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