1jrl: Difference between revisions

Revision as of 14:26, 21 February 2008

Crystal structure of E. coli Lysophospholiase L1/Acyl-CoA Thioesterase I/Protease I L109P mutant

OverviewOverview

Escherichia coli thioesterase I (TAP) is a multifunctional enzyme possessing activities of thioesterase, esterase, arylesterase, protease, and lysophospholipase. In particular, TAP has stereoselectivity for amino acid derivative substrates, hence it is useful for the kinetic resolution of racemic mixtures of industrial chemicals. In the present work, the crystal structure of native TAP was determined at 1.9A, revealing a minimal SGNH-hydrolase fold. The structure of TAP in complex with a diethyl phosphono moiety (DEP) identified its catalytic triad, Ser10-Asp154-His157, and oxyanion hole, Ser10-Gly44-Asn73. The oxyanion hole of TAP consists of three residues each separated from the other by more than 3.5A, implying that all of them are highly polarized when substrate bound. The catalytic (His)C(epsilon1)-H...O=C hydrogen bond usually plays a role in the catalytic mechanisms of most serine hydrolases, however, there were none present in SGNH-hydrolases. We propose that the existence of the highly polarized tri-residue-constituted oxyanion hole compensates for the lack of a (His)C(epsilon1)-H...O=C hydrogen bond. This suggests that members of the SGNH-hydrolase family may employ a unique catalytic mechanism. In addition, most SGNH-hydrolases have low sequence identities and presently there is no clear criterion to define consensus sequence blocks. Through comparison of TAP and the three SGNH-hydrolase structures currently known, we have identified a unique hydrogen bond network which stabilizes the catalytic center: a newly discovered structural feature of SGNH-hydrolases. We have defined these consensus sequence blocks providing a basis for the sub-classification of SGNH-hydrolases.

About this StructureAbout this Structure

1JRL is a Single protein structure of sequence from Escherichia coli with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of Escherichia coli thioesterase I/protease I/lysophospholipase L1: consensus sequence blocks constitute the catalytic center of SGNH-hydrolases through a conserved hydrogen bond network., Lo YC, Lin SC, Shaw JF, Liaw YC, J Mol Biol. 2003 Jul 11;330(3):539-51. PMID:12842470

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-[[Image:1jrl.jpg|left|200px]]<br /><applet load="1jrl" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1jrl.jpg|left|200px]]<br /><applet load="1jrl" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1jrl, resolution 1.95&Aring;" />
 '''Crystal structure of E. coli Lysophospholiase L1/Acyl-CoA Thioesterase I/Protease I L109P mutant'''<br />
 ==Overview==
-Escherichia coli thioesterase I (TAP) is a multifunctional enzyme, possessing activities of thioesterase, esterase, arylesterase, protease, and lysophospholipase. In particular, TAP has stereoselectivity for amino, acid derivative substrates, hence it is useful for the kinetic resolution, of racemic mixtures of industrial chemicals. In the present work, the, crystal structure of native TAP was determined at 1.9A, revealing a, minimal SGNH-hydrolase fold. The structure of TAP in complex with a, diethyl phosphono moiety (DEP) identified its catalytic triad, Ser10-Asp154-His157, and oxyanion hole, Ser10-Gly44-Asn73. The oxyanion, hole of TAP consists of three residues each separated from the other by, more than 3.5A, implying that all of them are highly polarized when, substrate bound. The catalytic (His)C(epsilon1)-H...O=C hydrogen bond, usually plays a role in the catalytic mechanisms of most serine, hydrolases, however, there were none present in SGNH-hydrolases. We, propose that the existence of the highly polarized tri-residue-constituted, oxyanion hole compensates for the lack of a (His)C(epsilon1)-H...O=C, hydrogen bond. This suggests that members of the SGNH-hydrolase family may, employ a unique catalytic mechanism. In addition, most SGNH-hydrolases, have low sequence identities and presently there is no clear criterion to, define consensus sequence blocks. Through comparison of TAP and the three, SGNH-hydrolase structures currently known, we have identified a unique, hydrogen bond network which stabilizes the catalytic center: a newly, discovered structural feature of SGNH-hydrolases. We have defined these, consensus sequence blocks providing a basis for the sub-classification of, SGNH-hydrolases.
+Escherichia coli thioesterase I (TAP) is a multifunctional enzyme possessing activities of thioesterase, esterase, arylesterase, protease, and lysophospholipase. In particular, TAP has stereoselectivity for amino acid derivative substrates, hence it is useful for the kinetic resolution of racemic mixtures of industrial chemicals. In the present work, the crystal structure of native TAP was determined at 1.9A, revealing a minimal SGNH-hydrolase fold. The structure of TAP in complex with a diethyl phosphono moiety (DEP) identified its catalytic triad, Ser10-Asp154-His157, and oxyanion hole, Ser10-Gly44-Asn73. The oxyanion hole of TAP consists of three residues each separated from the other by more than 3.5A, implying that all of them are highly polarized when substrate bound. The catalytic (His)C(epsilon1)-H...O=C hydrogen bond usually plays a role in the catalytic mechanisms of most serine hydrolases, however, there were none present in SGNH-hydrolases. We propose that the existence of the highly polarized tri-residue-constituted oxyanion hole compensates for the lack of a (His)C(epsilon1)-H...O=C hydrogen bond. This suggests that members of the SGNH-hydrolase family may employ a unique catalytic mechanism. In addition, most SGNH-hydrolases have low sequence identities and presently there is no clear criterion to define consensus sequence blocks. Through comparison of TAP and the three SGNH-hydrolase structures currently known, we have identified a unique hydrogen bond network which stabilizes the catalytic center: a newly discovered structural feature of SGNH-hydrolases. We have defined these consensus sequence blocks providing a basis for the sub-classification of SGNH-hydrolases.
 ==About this Structure==
-JRL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 and IMD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JRL OCA].
+JRL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=IMD:'>IMD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JRL OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Escherichia coli]]
 [[Category: Single protein]]
-[[Category: Liaw, Y.C.]]
+[[Category: Liaw, Y C.]]
-[[Category: Lin, S.C.]]
+[[Category: Lin, S C.]]
-[[Category: Lo, Y.C.]]
+[[Category: Lo, Y C.]]
-[[Category: Shaw, J.F.]]
+[[Category: Shaw, J F.]]
 [[Category: IMD]]
 [[Category: SO4]]
@@ Line 22: / Line 22: @@
 [[Category: protease]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:31:24 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:26:02 2008''