2rd5: Difference between revisions

Revision as of 19:46, 21 February 2008

Structural basis for the regulation of N-acetylglutamate kinase by PII in Arabidopsis thaliana

OverviewOverview

PII is a highly conserved regulatory protein found in organisms across the three domains of life. In cyanobacteria and plants, PII relieves the feedback inhibition of the rate-limiting step in arginine biosynthesis catalyzed by N-acetylglutamate kinase (NAGK). To understand the molecular structural basis of enzyme regulation by PII, we have determined a 2.5-A resolution crystal structure of a complex formed between two homotrimers of PII and a single hexamer of NAGK from Arabidopsis thaliana bound to the metabolites N-acetylglutamate, ADP, ATP, and arginine. In PII, the T-loop and Trp(22) at the start of the alpha1-helix, which are both adjacent to the ATP-binding site of PII, contact two beta-strands as well as the ends of two central helices (alphaE and alphaG) in NAGK, the opposing ends of which form major portions of the ATP and N-acetylglutamate substrate-binding sites. The binding of Mg(2+).ATP to PII stabilizes a conformation of the T-loop that favors interactions with both open and closed conformations of NAGK. Interactions between PII and NAGK appear to limit the degree of opening and closing of the active-site cleft in opposition to a domain-separating inhibitory effect exerted by arginine, thus explaining the stimulatory effect of PII on the kinetics of arginine-inhibited NAGK.

About this StructureAbout this Structure

2RD5 is a Protein complex structure of sequences from Arabidopsis thaliana with , , , and as ligands. Active as Acetylglutamate kinase, with EC number 2.7.2.8 Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for the regulation of N-acetylglutamate kinase by PII in Arabidopsis thaliana., Mizuno Y, Moorhead GB, Ng KK, J Biol Chem. 2007 Dec 7;282(49):35733-40. Epub 2007 Oct 3. PMID:17913711

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 ==Overview==
-PII is a highly conserved regulatory protein found in organisms across the, three domains of life. In cyanobacteria and plants, PII relieves the, feedback inhibition of the rate-limiting step in arginine biosynthesis, catalyzed by N-acetylglutamate kinase (NAGK). To understand the molecular, structural basis of enzyme regulation by PII, we have determined a 2.5-A, resolution crystal structure of a complex formed between two homotrimers, of PII and a single hexamer of NAGK from Arabidopsis thaliana bound to the, metabolites N-acetylglutamate, ADP, ATP, and arginine. In PII, the T-loop, and Trp(22) at the start of the alpha1-helix, which are both adjacent to, the ATP-binding site of PII, contact two beta-strands as well as the ends, of two central helices (alphaE and alphaG) in NAGK, the opposing ends of, which form major portions of the ATP and N-acetylglutamate, substrate-binding sites. The binding of Mg(2+).ATP to PII stabilizes a, conformation of the T-loop that favors interactions with both open and, closed conformations of NAGK. Interactions between PII and NAGK appear to, limit the degree of opening and closing of the active-site cleft in, opposition to a domain-separating inhibitory effect exerted by arginine, thus explaining the stimulatory effect of PII on the kinetics of, arginine-inhibited NAGK.
+PII is a highly conserved regulatory protein found in organisms across the three domains of life. In cyanobacteria and plants, PII relieves the feedback inhibition of the rate-limiting step in arginine biosynthesis catalyzed by N-acetylglutamate kinase (NAGK). To understand the molecular structural basis of enzyme regulation by PII, we have determined a 2.5-A resolution crystal structure of a complex formed between two homotrimers of PII and a single hexamer of NAGK from Arabidopsis thaliana bound to the metabolites N-acetylglutamate, ADP, ATP, and arginine. In PII, the T-loop and Trp(22) at the start of the alpha1-helix, which are both adjacent to the ATP-binding site of PII, contact two beta-strands as well as the ends of two central helices (alphaE and alphaG) in NAGK, the opposing ends of which form major portions of the ATP and N-acetylglutamate substrate-binding sites. The binding of Mg(2+).ATP to PII stabilizes a conformation of the T-loop that favors interactions with both open and closed conformations of NAGK. Interactions between PII and NAGK appear to limit the degree of opening and closing of the active-site cleft in opposition to a domain-separating inhibitory effect exerted by arginine, thus explaining the stimulatory effect of PII on the kinetics of arginine-inhibited NAGK.
 ==About this Structure==
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 ==Reference==
-Structural Basis for the Regulation of N-Acetylglutamate Kinase by PII in Arabidopsis thaliana., Mizuno Y, Moorhead GB, Ng KK, J Biol Chem. 2007 Dec 7;282(49):35733-40. Epub 2007 Oct 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17913711 17913711]
+Structural basis for the regulation of N-acetylglutamate kinase by PII in Arabidopsis thaliana., Mizuno Y, Moorhead GB, Ng KK, J Biol Chem. 2007 Dec 7;282(49):35733-40. Epub 2007 Oct 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17913711 17913711]
 [[Category: Acetylglutamate kinase]]
 [[Category: Arabidopsis thaliana]]
 [[Category: Protein complex]]
 [[Category: Mizuno, Y.]]
-[[Category: Moorhead, G.B.G.]]
+[[Category: Moorhead, G B.G.]]
-[[Category: Ng, K.K.S.]]
+[[Category: Ng, K K.S.]]
 [[Category: ADP]]
 [[Category: ARG]]
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 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:32:00 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:21 2008''