1u22: Difference between revisions

Revision as of 16:19, 21 February 2008

A. thaliana cobalamine independent methionine synthase

OverviewOverview

Cobalamin-independent methionine synthase (MetE) catalyzes the synthesis of methionine by a direct transfer of the methyl group of N5-methyltetrahydrofolate (CH3-H2PteGlun) to the sulfur atom of homocysteine (Hcy). We report here the first crystal structure of this metalloenzyme under different forms, free or complexed with the Hcy and folate substrates. The Arabidopsis thaliana MetE (AtMetE) crystals reveal a monomeric structure built by two (betaalpha)8 barrels making a deep groove at their interface. The active site is located at the surface of the C-terminal domain, facing the large interdomain cleft. Inside the active site, His647, Cys649, and Cys733 are involved in zinc coordination, whereas Asp605, Ile437, and Ser439 interact with Hcy. Opposite the zinc/Hcy binding site, a cationic loop (residues 507-529) belonging to the C-terminal domain anchors the first glutamyl residue of CH3-H4PteGlu5. The pterin moiety of CH3-H4PteGlu5 is stacked with Trp567, enabling the N5-methyl group to protrude in the direction of the zinc atom. These data suggest a structural role of the N-terminal domain of AtMetE in the stabilization of loop 507-529 and in the interaction with the poly-glutamate chain of CH3-H4PteGlun. Comparison of AtMetE structures reveals that the addition of Hcy does not lead to a direct coordination of the sulfur atom with zinc but to a reorganization of the zinc binding site with a stronger coordination to Cys649, Cys733, and a water molecule.

About this StructureAbout this Structure

1U22 is a Single protein structure of sequence from Arabidopsis thaliana with , , and as ligands. Active as 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase, with EC number 2.1.1.14 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of cobalamin-independent methionine synthase complexed with zinc, homocysteine, and methyltetrahydrofolate., Ferrer JL, Ravanel S, Robert M, Dumas R, J Biol Chem. 2004 Oct 22;279(43):44235-8. Epub 2004 Aug 23. PMID:15326182

Page seeded by OCA on Thu Feb 21 15:19:48 2008

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OCA

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-[[Image:1u22.gif|left|200px]]<br /><applet load="1u22" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1u22.gif|left|200px]]<br /><applet load="1u22" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1u22, resolution 2.65&Aring;" />
 '''A. thaliana cobalamine independent methionine synthase'''<br />
 ==Overview==
-Cobalamin-independent methionine synthase (MetE) catalyzes the synthesis, of methionine by a direct transfer of the methyl group of, N5-methyltetrahydrofolate (CH3-H2PteGlun) to the sulfur atom of, homocysteine (Hcy). We report here the first crystal structure of this, metalloenzyme under different forms, free or complexed with the Hcy and, folate substrates. The Arabidopsis thaliana MetE (AtMetE) crystals reveal, a monomeric structure built by two (betaalpha)8 barrels making a deep, groove at their interface. The active site is located at the surface of, the C-terminal domain, facing the large interdomain cleft. Inside the, active site, His647, Cys649, and Cys733 are involved in zinc coordination, whereas Asp605, Ile437, and Ser439 interact with Hcy. Opposite the, zinc/Hcy binding site, a cationic loop (residues 507-529) belonging to the, C-terminal domain anchors the first glutamyl residue of CH3-H4PteGlu5. The, pterin moiety of CH3-H4PteGlu5 is stacked with Trp567, enabling the, N5-methyl group to protrude in the direction of the zinc atom. These data, suggest a structural role of the N-terminal domain of AtMetE in the, stabilization of loop 507-529 and in the interaction with the, poly-glutamate chain of CH3-H4PteGlun. Comparison of AtMetE structures, reveals that the addition of Hcy does not lead to a direct coordination of, the sulfur atom with zinc but to a reorganization of the zinc binding site, with a stronger coordination to Cys649, Cys733, and a water molecule.
+Cobalamin-independent methionine synthase (MetE) catalyzes the synthesis of methionine by a direct transfer of the methyl group of N5-methyltetrahydrofolate (CH3-H2PteGlun) to the sulfur atom of homocysteine (Hcy). We report here the first crystal structure of this metalloenzyme under different forms, free or complexed with the Hcy and folate substrates. The Arabidopsis thaliana MetE (AtMetE) crystals reveal a monomeric structure built by two (betaalpha)8 barrels making a deep groove at their interface. The active site is located at the surface of the C-terminal domain, facing the large interdomain cleft. Inside the active site, His647, Cys649, and Cys733 are involved in zinc coordination, whereas Asp605, Ile437, and Ser439 interact with Hcy. Opposite the zinc/Hcy binding site, a cationic loop (residues 507-529) belonging to the C-terminal domain anchors the first glutamyl residue of CH3-H4PteGlu5. The pterin moiety of CH3-H4PteGlu5 is stacked with Trp567, enabling the N5-methyl group to protrude in the direction of the zinc atom. These data suggest a structural role of the N-terminal domain of AtMetE in the stabilization of loop 507-529 and in the interaction with the poly-glutamate chain of CH3-H4PteGlun. Comparison of AtMetE structures reveals that the addition of Hcy does not lead to a direct coordination of the sulfur atom with zinc but to a reorganization of the zinc binding site with a stronger coordination to Cys649, Cys733, and a water molecule.
 ==About this Structure==
-U22 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] with ZN, SO4, HCS and THG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/5-methyltetrahydropteroyltriglutamate--homocysteine_S-methyltransferase 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.14 2.1.1.14] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U22 OCA].
+U22 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=HCS:'>HCS</scene> and <scene name='pdbligand=THG:'>THG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/5-methyltetrahydropteroyltriglutamate--homocysteine_S-methyltransferase 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.14 2.1.1.14] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U22 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Dumas, R.]]
-[[Category: Ferrer, J.L.]]
+[[Category: Ferrer, J L.]]
 [[Category: Ravanel, S.]]
 [[Category: Robert, M.]]
@@ Line 27: / Line 27: @@
 [[Category: synthase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:47:19 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:48 2008''