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1tmm

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{{STRUCTURE_1tmm| PDB=1tmm | SCENE= }}
{{STRUCTURE_1tmm| PDB=1tmm | SCENE= }}
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'''Crystal structure of ternary complex of E.coli HPPK(W89A) with MGAMPCPP and 6-Hydroxymethylpterin'''
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===Crystal structure of ternary complex of E.coli HPPK(W89A) with MGAMPCPP and 6-Hydroxymethylpterin===
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==Overview==
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Deletion mutagenesis, biochemical, and X-ray crystallographic studies have shown that loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is required for the assembly of the active center, plays an important role in the stabilization of the ternary complex of HPPK with MgATP and 6-hydroxymethyl-7,8-dihydropterin (HP), and is essential for catalysis. Whether the critical functional importance of loop 3 is due to the interactions between residues R84 and W89 and the two substrates has been addressed by site-directed mutagenesis, biochemical, and X-ray crystallographic studies. Substitution of R84 with alanine causes little changes in the dissociation constants and kinetic constants of the HPPK-catalyzed reaction, indicating that R84 is not important for either substrate binding or catalysis. Substitution of W89 with alanine increases the K(d) for the binding of MgATP by a factor of 3, whereas the K(d) for HP increases by a factor of 6, which is due to the increase in the dissociation rate constant. The W89A mutation decreases the rate constant for the chemical step of the forward reaction by a factor of 15 and the rate constant for the chemical step of the reverse reaction by a factor of 25. The biochemical results of the W89A mutation indicate that W89 contributes somewhat to the binding of HP and more significantly to the chemical step. The crystal structures of W89A show that W89A has different conformations in loops 2 and 3, but the critical catalytic residues are positioned for catalysis. When these results are taken together, they suggest that the critical functional importance of loop 3 is not due to the interactions of the R84 guanidinium group or the W89 indole ring with the substrates.
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(as it appears on PubMed at http://www.pubmed.gov), where 15952765 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15952765}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84 and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic studies., Li Y, Blaszczyk J, Wu Y, Shi G, Ji X, Yan H, Biochemistry. 2005 Jun 21;44(24):8590-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15952765 15952765]
Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84 and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic studies., Li Y, Blaszczyk J, Wu Y, Shi G, Ji X, Yan H, Biochemistry. 2005 Jun 21;44(24):8590-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15952765 15952765]
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Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents., Xiao B, Shi G, Chen X, Yan H, Ji X, Structure. 1999 May;7(5):489-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10378268 10378268]
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Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution., Blaszczyk J, Shi G, Yan H, Ji X, Structure. 2000 Oct 15;8(10):1049-58. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11080626 11080626]
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Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies., Shi G, Blaszczyk J, Ji X, Yan H, J Med Chem. 2001 Apr 26;44(9):1364-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11311059 11311059]
[[Category: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase]]
[[Category: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase]]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Ternary complex]]
[[Category: Ternary complex]]
[[Category: X-ray crystallography]]
[[Category: X-ray crystallography]]
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Revision as of 11:29, 29 July 2008

Image:1tmm.png

Template:STRUCTURE 1tmm

Crystal structure of ternary complex of E.coli HPPK(W89A) with MGAMPCPP and 6-Hydroxymethylpterin

Template:ABSTRACT PUBMED 15952765

About this Structure

1TMM is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84 and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic studies., Li Y, Blaszczyk J, Wu Y, Shi G, Ji X, Yan H, Biochemistry. 2005 Jun 21;44(24):8590-9. PMID:15952765

Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents., Xiao B, Shi G, Chen X, Yan H, Ji X, Structure. 1999 May;7(5):489-96. PMID:10378268

Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution., Blaszczyk J, Shi G, Yan H, Ji X, Structure. 2000 Oct 15;8(10):1049-58. PMID:11080626

Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies., Shi G, Blaszczyk J, Ji X, Yan H, J Med Chem. 2001 Apr 26;44(9):1364-71. PMID:11311059

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