2huu: Difference between revisions

Revision as of 18:46, 21 February 2008

Crystal structure of Aedes aegypti alanine glyoxylate aminotransferase in complex with alanine

OverviewOverview

Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75A high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.

About this StructureAbout this Structure

2HUU is a Single protein structure of sequence from Aedes aegypti with and as ligands. Active as Alanine--glyoxylate transaminase, with EC number 2.6.1.44 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase., Han Q, Robinson H, Gao YG, Vogelaar N, Wilson SR, Rizzi M, Li J, J Biol Chem. 2006 Dec 1;281(48):37175-82. Epub 2006 Sep 21. PMID:16990263

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 ==Overview==
-Mosquitoes are unique in having evolved two alanine glyoxylate, aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of, 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is, used by malaria parasites as a chemical trigger for their development, within the mosquito. This 3-HK to XA conversion is considered the major, mechanism mosquitoes use to detoxify the chemically reactive and, potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and, is specific for converting glyoxylic acid to glycine. Here we report the, 1.75A high-resolution three-dimensional crystal structure of AGT from the, mosquito Aedes aegypti (AeAGT) and structures of its complexes with, reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal, structures of an AGT with its amino acceptor, glyoxylic acid, and amino, donor, alanine, have been determined. The protein is dimeric and adopts, the type I-fold of pyridoxal 5-phosphate (PLP)-dependent, aminotransferases. The PLP co-factor is covalently bound to the active, site in the crystal structure, and its binding site is similar to those of, other AGTs. The comparison of the AeAGT-glyoxylic acid structure with, other AGT structures revealed that these glyoxylic acid binding residues, are conserved in most AGTs. Comparison of the AeAGT-alanine structure with, that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe, motif in the latter may be responsible for the substrate specificity of, HKT enzymes for 3-HK.
+Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75A high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.
 ==About this Structure==
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 [[Category: Alanine--glyoxylate transaminase]]
 [[Category: Single protein]]
-[[Category: Gao, Y.G.]]
+[[Category: Gao, Y G.]]
 [[Category: Han, Q.]]
 [[Category: Li, J.]]
@@ Line 20: / Line 20: @@
 [[Category: Robinson, H.]]
 [[Category: Vogelaar, N.]]
-[[Category: Wilson, S.R.]]
+[[Category: Wilson, S R.]]
 [[Category: 1BO]]
 [[Category: ALA]]
@@ Line 26: / Line 26: @@
 [[Category: plp-dependent transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:29:24 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:45:58 2008''