1ig0
From Proteopedia
(New page: 200px<br /><applet load="1ig0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ig0, resolution 1.80Å" /> '''Crystal Structure of...) |
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| - | [[Image:1ig0.gif|left|200px]]<br /><applet load="1ig0" size=" | + | [[Image:1ig0.gif|left|200px]]<br /><applet load="1ig0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ig0, resolution 1.80Å" /> | caption="1ig0, resolution 1.80Å" /> | ||
'''Crystal Structure of yeast Thiamin Pyrophosphokinase'''<br /> | '''Crystal Structure of yeast Thiamin Pyrophosphokinase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Thiamin pyrophosphokinase (TPK) catalyzes the transfer of a | + | BACKGROUND: Thiamin pyrophosphokinase (TPK) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. TPK has no sequence homologs in the PDB and functions by an unknown mechanism. The TPK structure has been determined as a significant step toward elucidating its catalytic action. RESULTS: The crystal structure of Saccharomyces cerevisiae TPK complexed with thiamin has been determined at 1.8 A resolution. TPK is a homodimer, and each subunit consists of two domains. One domain resembles a Rossman fold with four alpha helices on each side of a 6 strand parallel beta sheet. The other domain has one 4 strand and one 6 strand antiparallel beta sheet, which form a flattened sandwich structure containing a jelly-roll topology. The active site is located in a cleft at the dimer interface and is formed from residues from domains of both subunits. The TPK dimer contains two compound active sites at the subunit interface. CONCLUSIONS: The structure of TPK with one substrate bound identifies the location of the thiamin binding site and probable catalytic residues. The structure also suggests a likely binding site for ATP. These findings are further supported by TPK sequence homologies. Although possessing no significant sequence homology with other pyrophospokinases, thiamin pyrophosphokinase may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis. |
==About this Structure== | ==About this Structure== | ||
| - | 1IG0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with VIB as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thiamine_diphosphokinase Thiamine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.2 2.7.6.2] Full crystallographic information is available from [http:// | + | 1IG0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=VIB:'>VIB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thiamine_diphosphokinase Thiamine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.2 2.7.6.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IG0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thiamine diphosphokinase]] | [[Category: Thiamine diphosphokinase]] | ||
| - | [[Category: Baker, L | + | [[Category: Baker, L J.]] |
| - | [[Category: Dorocke, J | + | [[Category: Dorocke, J A.]] |
| - | [[Category: Harris, R | + | [[Category: Harris, R A.]] |
| - | [[Category: Timm, D | + | [[Category: Timm, D E.]] |
[[Category: VIB]] | [[Category: VIB]] | ||
[[Category: alpha-beta-alpha]] | [[Category: alpha-beta-alpha]] | ||
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[[Category: protein-substrate complex]] | [[Category: protein-substrate complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:11:32 2008'' |
Revision as of 11:11, 21 February 2008
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Crystal Structure of yeast Thiamin Pyrophosphokinase
Overview
BACKGROUND: Thiamin pyrophosphokinase (TPK) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. TPK has no sequence homologs in the PDB and functions by an unknown mechanism. The TPK structure has been determined as a significant step toward elucidating its catalytic action. RESULTS: The crystal structure of Saccharomyces cerevisiae TPK complexed with thiamin has been determined at 1.8 A resolution. TPK is a homodimer, and each subunit consists of two domains. One domain resembles a Rossman fold with four alpha helices on each side of a 6 strand parallel beta sheet. The other domain has one 4 strand and one 6 strand antiparallel beta sheet, which form a flattened sandwich structure containing a jelly-roll topology. The active site is located in a cleft at the dimer interface and is formed from residues from domains of both subunits. The TPK dimer contains two compound active sites at the subunit interface. CONCLUSIONS: The structure of TPK with one substrate bound identifies the location of the thiamin binding site and probable catalytic residues. The structure also suggests a likely binding site for ATP. These findings are further supported by TPK sequence homologies. Although possessing no significant sequence homology with other pyrophospokinases, thiamin pyrophosphokinase may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis.
About this Structure
1IG0 is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Thiamine diphosphokinase, with EC number 2.7.6.2 Full crystallographic information is available from OCA.
Reference
The crystal structure of yeast thiamin pyrophosphokinase., Baker LJ, Dorocke JA, Harris RA, Timm DE, Structure. 2001 Jun;9(6):539-46. PMID:11435118
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