1hq2
From Proteopedia
(New page: 200px<br /><applet load="1hq2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hq2, resolution 1.25Å" /> '''CRYSTAL STRUCTURE OF...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1hq2.gif|left|200px]]<br /><applet load="1hq2" size=" | + | [[Image:1hq2.gif|left|200px]]<br /><applet load="1hq2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hq2, resolution 1.25Å" /> | caption="1hq2, resolution 1.25Å" /> | ||
'''CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E.COLI HPPK(R82A) WITH MGAMPCPP AND 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN AT 1.25 ANGSTROM RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E.COLI HPPK(R82A) WITH MGAMPCPP AND 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN AT 1.25 ANGSTROM RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the | + | 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. Arginine residues 82 and 92, strictly conserved in 35 HPPK sequences, play dynamic roles in the catalytic cycle of the enzyme. At 0.89-A resolution, two distinct conformations are observed for each of the two residues in the crystal structure of the wild-type HPPK in complex with two HP variants, two Mg(2+) ions, and an ATP analogue. Structural information suggests that R92 first binds to the alpha-phosphate group of ATP and then shifts to interact with the beta-phosphate as R82, which initially does not bind to ATP, moves in and binds to alpha-phosphate when the pyrophosphoryl transfer is about to occur. The dynamic roles of R82 and R92 are further elucidated by five more crystal structures of two mutant proteins, R82A and R92A, with and without bound ligands. Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-A structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89. |
==About this Structure== | ==About this Structure== | ||
| - | 1HQ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG, CL, ACT, APC and PH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2-amino-4-hydroxy-6-hydroxymethyldihydropteridine_diphosphokinase 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.3 2.7.6.3] Full crystallographic information is available from [http:// | + | 1HQ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=APC:'>APC</scene> and <scene name='pdbligand=PH2:'>PH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2-amino-4-hydroxy-6-hydroxymethyldihydropteridine_diphosphokinase 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.3 2.7.6.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HQ2 OCA]. |
==Reference== | ==Reference== | ||
| Line 35: | Line 35: | ||
[[Category: x-ray crystallography]] | [[Category: x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:03:43 2008'' |
Revision as of 11:03, 21 February 2008
|
CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E.COLI HPPK(R82A) WITH MGAMPCPP AND 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN AT 1.25 ANGSTROM RESOLUTION
Overview
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. Arginine residues 82 and 92, strictly conserved in 35 HPPK sequences, play dynamic roles in the catalytic cycle of the enzyme. At 0.89-A resolution, two distinct conformations are observed for each of the two residues in the crystal structure of the wild-type HPPK in complex with two HP variants, two Mg(2+) ions, and an ATP analogue. Structural information suggests that R92 first binds to the alpha-phosphate group of ATP and then shifts to interact with the beta-phosphate as R82, which initially does not bind to ATP, moves in and binds to alpha-phosphate when the pyrophosphoryl transfer is about to occur. The dynamic roles of R82 and R92 are further elucidated by five more crystal structures of two mutant proteins, R82A and R92A, with and without bound ligands. Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-A structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89.
About this Structure
1HQ2 is a Single protein structure of sequence from Escherichia coli with , , , and as ligands. Active as 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase, with EC number 2.7.6.3 Full crystallographic information is available from OCA.
Reference
Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies., Blaszczyk J, Li Y, Shi G, Yan H, Ji X, Biochemistry. 2003 Feb 18;42(6):1573-80. PMID:12578370
Page seeded by OCA on Thu Feb 21 13:03:43 2008
Categories: 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase | Escherichia coli | Single protein | Blaszczyk, J. | Ji, X. | ACT | APC | CL | MG | PH2 | 6-hydroxymethyl-7 | 8-dihydropterin | Antimicrobial agent | Catalytic mechanism | Drug design | Folate | Hppk | Pterin | Pyrophosphokinase | Pyrophosphoryl transfer | Substrate specificity | Ternary complex | X-ray crystallography
