1ju4: Difference between revisions

Revision as of 14:26, 21 February 2008

BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT

OverviewOverview

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 StructureAbout this Structure

1JU4 is a Single protein structure of sequence from Rhodococcus sp. mb1 with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

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

Page seeded by OCA on Thu Feb 21 13:26:53 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:1ju4.jpg|left|200px]]<br /><applet load="1ju4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ju4.jpg|left|200px]]<br /><applet load="1ju4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1ju4, resolution 1.63&Aring;" />
 '''BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT'''<br />
 ==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.
+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==
-JU4 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 BEZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JU4 OCA].
+JU4 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=BEZ:'>BEZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JU4 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Basran, A.]]
-[[Category: Bruce, N.C.]]
+[[Category: Bruce, N C.]]
-[[Category: Larsen, N.A.]]
+[[Category: Larsen, N A.]]
-[[Category: Lerner, R.A.]]
+[[Category: Lerner, R A.]]
-[[Category: Rosser, S.J.]]
+[[Category: Rosser, S J.]]
 [[Category: Stevens, J.]]
-[[Category: Turner, J.M.]]
+[[Category: Turner, J M.]]
-[[Category: Wilson, I.A.]]
+[[Category: Wilson, I A.]]
 [[Category: BEZ]]
 [[Category: alpha/beta hydrolase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:34:47 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:26:53 2008''