2nw8: Difference between revisions

Revision as of 19:11, 21 February 2008

Crystal Structure of Tryptophan 2,3-dioxygenase (TDO) from Xanthomonas campestris in complex with ferrous heme and tryptophan. Northeast Structural Genomics Target XcR13.

OverviewOverview

Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) constitute an important, yet relatively poorly understood, family of heme-containing enzymes. Here, we report extensive structural and biochemical studies of the Xanthomonas campestris TDO and a related protein SO4414 from Shewanella oneidensis, including the structure at 1.6-A resolution of the catalytically active, ferrous form of TDO in a binary complex with the substrate L-Trp. The carboxylate and ammonium moieties of tryptophan are recognized by electrostatic and hydrogen-bonding interactions with the enzyme and a propionate group of the heme, thus defining the L-stereospecificity. A second, possibly allosteric, L-Trp-binding site is present at the tetramer interface. The sixth coordination site of the heme-iron is vacant, providing a dioxygen-binding site that would also involve interactions with the ammonium moiety of L-Trp and the amide nitrogen of a glycine residue. The indole ring is positioned correctly for oxygenation at the C2 and C3 atoms. The active site is fully formed only in the binary complex, and biochemical experiments confirm this induced-fit behavior of the enzyme. The active site is completely devoid of water during catalysis, which is supported by our electrochemical studies showing significant stabilization of the enzyme upon substrate binding.

About this StructureAbout this Structure

2NW8 is a Single protein structure of sequence from Xanthomonas campestris pv. campestris with , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase., Forouhar F, Anderson JL, Mowat CG, Vorobiev SM, Hussain A, Abashidze M, Bruckmann C, Thackray SJ, Seetharaman J, Tucker T, Xiao R, Ma LC, Zhao L, Acton TB, Montelione GT, Chapman SK, Tong L, Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):473-8. Epub 2006 Dec 29. PMID:17197414

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OCA

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 ==Overview==
-Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), constitute an important, yet relatively poorly understood, family of, heme-containing enzymes. Here, we report extensive structural and, biochemical studies of the Xanthomonas campestris TDO and a related, protein SO4414 from Shewanella oneidensis, including the structure at, 1.6-A resolution of the catalytically active, ferrous form of TDO in a, binary complex with the substrate L-Trp. The carboxylate and ammonium, moieties of tryptophan are recognized by electrostatic and, hydrogen-bonding interactions with the enzyme and a propionate group of, the heme, thus defining the L-stereospecificity. A second, possibly, allosteric, L-Trp-binding site is present at the tetramer interface. The, sixth coordination site of the heme-iron is vacant, providing a, dioxygen-binding site that would also involve interactions with the, ammonium moiety of L-Trp and the amide nitrogen of a glycine residue. The, indole ring is positioned correctly for oxygenation at the C2 and C3, atoms. The active site is fully formed only in the binary complex, and, biochemical experiments confirm this induced-fit behavior of the enzyme., The active site is completely devoid of water during catalysis, which is, supported by our electrochemical studies showing significant stabilization, of the enzyme upon substrate binding.
+Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) constitute an important, yet relatively poorly understood, family of heme-containing enzymes. Here, we report extensive structural and biochemical studies of the Xanthomonas campestris TDO and a related protein SO4414 from Shewanella oneidensis, including the structure at 1.6-A resolution of the catalytically active, ferrous form of TDO in a binary complex with the substrate L-Trp. The carboxylate and ammonium moieties of tryptophan are recognized by electrostatic and hydrogen-bonding interactions with the enzyme and a propionate group of the heme, thus defining the L-stereospecificity. A second, possibly allosteric, L-Trp-binding site is present at the tetramer interface. The sixth coordination site of the heme-iron is vacant, providing a dioxygen-binding site that would also involve interactions with the ammonium moiety of L-Trp and the amide nitrogen of a glycine residue. The indole ring is positioned correctly for oxygenation at the C2 and C3 atoms. The active site is fully formed only in the binary complex, and biochemical experiments confirm this induced-fit behavior of the enzyme. The active site is completely devoid of water during catalysis, which is supported by our electrochemical studies showing significant stabilization of the enzyme upon substrate binding.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Single protein]]
 [[Category: Xanthomonas campestris pv. campestris]]
-[[Category: Acton, T.B.]]
+[[Category: Acton, T B.]]
-[[Category: Anderson, J.L.R.]]
+[[Category: Anderson, J L.R.]]
-[[Category: Baran, M.C.]]
+[[Category: Baran, M C.]]
 [[Category: Bruckmann, C.]]
-[[Category: Champman, S.K.]]
+[[Category: Champman, S K.]]
 [[Category: Cunningham, K.]]
 [[Category: Forouhar, F.]]
-[[Category: Ho, C.K.]]
+[[Category: Ho, C K.]]
 [[Category: Janjua, H.]]
 [[Category: Liu, J.]]
-[[Category: Ma, L.C.]]
+[[Category: Ma, L C.]]
-[[Category: Montelione, G.T.]]
+[[Category: Montelione, G T.]]
-[[Category: Mowat, C.G.]]
+[[Category: Mowat, C G.]]
-[[Category: NESG, Northeast.Structural.Genomics.Consortium.]]
+[[Category: NESG, Northeast Structural Genomics Consortium.]]
 [[Category: Rost, B.]]
 [[Category: Seetharaman, J.]]
-[[Category: Thackray, S.J.]]
+[[Category: Thackray, S J.]]
 [[Category: Tong, L.]]
 [[Category: Xiao, R.]]
@@ Line 43: / Line 43: @@
 [[Category: structural genomics]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:00:41 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:11:42 2008''