1f9z: Difference between revisions

Revision as of 13:36, 21 February 2008

CRYSTAL STRUCTURE OF THE NI(II)-BOUND GLYOXALASE I FROM ESCHERICHIA COLI

OverviewOverview

The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically produced hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-D-lactoylglutathione. Human GlxI, for which the structure is known, is active in the presence of Zn(2+). Unexpectedly, the Escherichia coli enzyme is inactive in the presence of Zn(2+) and is maximally active with Ni(2+). To understand this difference in metal activation and also to obtain a representative of the bacterial enzymes, the structure of E. coli Ni(2+)-GlxI has been determined. Structures have also been determined for the apo enzyme as well as complexes with Co(2+), Cd(2+), and Zn(2+). It is found that each of the protein-metal complexes that is catalytically active has octahedral geometry. This includes the complexes of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported for the human Zn(2+) enzyme. Conversely, the complex of the E. coli enzyme with Zn(2+) has trigonal bipyramidal coordination and is inactive. This mode of coordination includes four protein ligands plus a single water molecule. In contrast, the coordination in the active forms of the enzyme includes two water molecules bound to the metal ion, suggesting that this may be a key feature of the catalytic mechanism. A comparison of the human and E. coli enzymes suggests that there are differences between the active sites that might be exploited for therapeutic use.

About this StructureAbout this Structure

1F9Z is a Single protein structure of sequence from Escherichia coli with as ligand. Active as Lactoylglutathione lyase, with EC number 4.4.1.5 Full crystallographic information is available from OCA.

ReferenceReference

Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation., He MM, Clugston SL, Honek JF, Matthews BW, Biochemistry. 2000 Aug 1;39(30):8719-27. PMID:10913283

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-[[Image:1f9z.jpg|left|200px]]<br /><applet load="1f9z" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1f9z.jpg|left|200px]]<br /><applet load="1f9z" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1f9z, resolution 1.5&Aring;" />
 '''CRYSTAL STRUCTURE OF THE NI(II)-BOUND GLYOXALASE I FROM ESCHERICHIA COLI'''<br />
 ==Overview==
-The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically, produced hemimercaptal of cytotoxic methylglyoxal and glutathione to, nontoxic S-D-lactoylglutathione. Human GlxI, for which the structure is, known, is active in the presence of Zn(2+). Unexpectedly, the Escherichia, coli enzyme is inactive in the presence of Zn(2+) and is maximally active, with Ni(2+). To understand this difference in metal activation and also to, obtain a representative of the bacterial enzymes, the structure of E. coli, Ni(2+)-GlxI has been determined. Structures have also been determined for, the apo enzyme as well as complexes with Co(2+), Cd(2+), and Zn(2+). It is, found that each of the protein-metal complexes that is catalytically, active has octahedral geometry. This includes the complexes of the E. coli, enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported, for the human Zn(2+) enzyme. Conversely, the complex of the E. coli enzyme, with Zn(2+) has trigonal bipyramidal coordination and is inactive. This, mode of coordination includes four protein ligands plus a single water, molecule. In contrast, the coordination in the active forms of the enzyme, includes two water molecules bound to the metal ion, suggesting that this, may be a key feature of the catalytic mechanism. A comparison of the human, and E. coli enzymes suggests that there are differences between the active, sites that might be exploited for therapeutic use.
+The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically produced hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-D-lactoylglutathione. Human GlxI, for which the structure is known, is active in the presence of Zn(2+). Unexpectedly, the Escherichia coli enzyme is inactive in the presence of Zn(2+) and is maximally active with Ni(2+). To understand this difference in metal activation and also to obtain a representative of the bacterial enzymes, the structure of E. coli Ni(2+)-GlxI has been determined. Structures have also been determined for the apo enzyme as well as complexes with Co(2+), Cd(2+), and Zn(2+). It is found that each of the protein-metal complexes that is catalytically active has octahedral geometry. This includes the complexes of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported for the human Zn(2+) enzyme. Conversely, the complex of the E. coli enzyme with Zn(2+) has trigonal bipyramidal coordination and is inactive. This mode of coordination includes four protein ligands plus a single water molecule. In contrast, the coordination in the active forms of the enzyme includes two water molecules bound to the metal ion, suggesting that this may be a key feature of the catalytic mechanism. A comparison of the human and E. coli enzymes suggests that there are differences between the active sites that might be exploited for therapeutic use.
 ==About this Structure==
-F9Z 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 NI as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Lactoylglutathione_lyase Lactoylglutathione lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.5 4.4.1.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1F9Z OCA].
+F9Z 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=NI:'>NI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Lactoylglutathione_lyase Lactoylglutathione lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.5 4.4.1.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F9Z OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Lactoylglutathione lyase]]
 [[Category: Single protein]]
-[[Category: Clugston, S.L.]]
+[[Category: Clugston, S L.]]
-[[Category: He, M.M.]]
+[[Category: He, M M.]]
-[[Category: Honek, J.F.]]
+[[Category: Honek, J F.]]
-[[Category: Matthews, B.W.]]
+[[Category: Matthews, B W.]]
 [[Category: NI]]
 [[Category: beta-alpha-beta-beta-beta motif]]
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 [[Category: protein-ni(ii) complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 14:44:57 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:34 2008''