1epv
From Proteopedia
(New page: 200px<br /><applet load="1epv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1epv, resolution 2.20Å" /> '''ALANINE RACEMASE WIT...) |
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| - | [[Image:1epv.gif|left|200px]]<br /><applet load="1epv" size=" | + | [[Image:1epv.gif|left|200px]]<br /><applet load="1epv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1epv, resolution 2.20Å" /> | caption="1epv, resolution 2.20Å" /> | ||
'''ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE'''<br /> | '''ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine | + | Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine enantiomers, and thus represents the first committed step involved in bacterial cell wall biosynthesis. Cycloserine acts as a suicide inhibitor of alanine racemase and as such, serves as an antimicrobial agent. The chemical means by which cycloserine inhibits alanine racemase is unknown. Through spectroscopic assays, we show here evidence of a pyridoxal derivative (arising from either isomer of cycloserine) saturated at the C4' carbon position. We additionally report the L- and D-cycloserine inactivated crystal structures of Bacillus stearothermophilus alanine racemase, which corroborates the spectroscopy via evidence of a 3-hydroxyisoxazole pyridoxamine derivative. Upon the basis of the kinetic and structural properties of both the L- and D-isomers of the inhibitor, we propose a mechanism of alanine racemase inactivation by cycloserine. This pathway involves an initial transamination step followed by tautomerization to form a stable aromatic adduct, a scheme similar to that seen in cycloserine inactivation of aminotransferases. |
==About this Structure== | ==About this Structure== | ||
| - | 1EPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with DCS as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Full crystallographic information is available from [http:// | + | 1EPV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=DCS:'>DCS</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EPV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Geobacillus stearothermophilus]] | [[Category: Geobacillus stearothermophilus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fenn, T | + | [[Category: Fenn, T D.]] |
| - | [[Category: Morollo, A | + | [[Category: Morollo, A A.]] |
[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
| - | [[Category: Stamper, G | + | [[Category: Stamper, G F.]] |
[[Category: DCS]] | [[Category: DCS]] | ||
[[Category: alpha-beta barrel]] | [[Category: alpha-beta barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:30:24 2008'' |
Revision as of 10:30, 21 February 2008
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ALANINE RACEMASE WITH BOUND INHIBITOR DERIVED FROM D-CYCLOSERINE
Overview
Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine enantiomers, and thus represents the first committed step involved in bacterial cell wall biosynthesis. Cycloserine acts as a suicide inhibitor of alanine racemase and as such, serves as an antimicrobial agent. The chemical means by which cycloserine inhibits alanine racemase is unknown. Through spectroscopic assays, we show here evidence of a pyridoxal derivative (arising from either isomer of cycloserine) saturated at the C4' carbon position. We additionally report the L- and D-cycloserine inactivated crystal structures of Bacillus stearothermophilus alanine racemase, which corroborates the spectroscopy via evidence of a 3-hydroxyisoxazole pyridoxamine derivative. Upon the basis of the kinetic and structural properties of both the L- and D-isomers of the inhibitor, we propose a mechanism of alanine racemase inactivation by cycloserine. This pathway involves an initial transamination step followed by tautomerization to form a stable aromatic adduct, a scheme similar to that seen in cycloserine inactivation of aminotransferases.
About this Structure
1EPV is a Single protein structure of sequence from Geobacillus stearothermophilus with as ligand. Active as Alanine racemase, with EC number 5.1.1.1 Full crystallographic information is available from OCA.
Reference
A side reaction of alanine racemase: transamination of cycloserine., Fenn TD, Stamper GF, Morollo AA, Ringe D, Biochemistry. 2003 May 20;42(19):5775-83. PMID:12741835
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