2get
From Proteopedia
(New page: 200px<br /><applet load="2get" size="450" color="white" frame="true" align="right" spinBox="true" caption="2get, resolution 2.35Å" /> '''Pantothenate kinase ...) |
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| - | [[Image:2get.gif|left|200px]]<br /><applet load="2get" size=" | + | [[Image:2get.gif|left|200px]]<br /><applet load="2get" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2get, resolution 2.35Å" /> | caption="2get, resolution 2.35Å" /> | ||
'''Pantothenate kinase from Mycobacterium tuberculosis (MtPanK) in complex with a coenzyme A derivative, Form-I (LT)'''<br /> | '''Pantothenate kinase from Mycobacterium tuberculosis (MtPanK) in complex with a coenzyme A derivative, Form-I (LT)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pantothenate kinase (PanK) is a ubiquitous and essential enzyme that | + | Pantothenate kinase (PanK) is a ubiquitous and essential enzyme that catalyzes the first step of the universal coenzyme A biosynthetic pathway. In this step, pantothenate (vitamin B(5)) is converted to 4'-phosphopantothenate, which subsequently forms coenzyme A in four enzymatic steps. The complex of this enzyme from Mycobacterium tuberculosis (MtPanK) with a derivative of the feedback inhibitor coenzyme A has been crystallized in two forms and its structure solved. The structure was refined in both forms using room-temperature and low-temperature X-ray data. In both forms, the MtPanK subunit has a mononucleotide-binding fold with a seven-stranded central beta-sheet and helices on either side. However, there is a small though significant difference in subunit association between the two forms. The structure is also grossly similar to the enzyme from Escherichia coli. The active-site pocket and the dimeric interface are on two opposite sides of the PanK subunit. The enzymes from M. tuberculosis and E. coli exhibit several differences, particularly at the dimeric interface. On the other hand, the coenzyme A-binding region is almost entirely conserved. A delineation of the invariant and variable features of the PanK structure further indicates that the dimeric interface is very variable, while the coenzyme A-binding site is substantially invariant. A sequence alignment involving various bacterial PanKs is in agreement with this conclusion. The strong correlation between structural plasticity, evolutionary conservation and variability and function exhibited by the molecule could be important in the design of species-specific inhibitors of the enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 2GET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with COK and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pantothenate_kinase Pantothenate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.33 2.7.1.33] Full crystallographic information is available from [http:// | + | 2GET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=COK:'>COK</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pantothenate_kinase Pantothenate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.33 2.7.1.33] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GET OCA]. |
==Reference== | ==Reference== | ||
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[[Category: nucleotide binding]] | [[Category: nucleotide binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:58 2008'' |
Revision as of 15:31, 21 February 2008
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Pantothenate kinase from Mycobacterium tuberculosis (MtPanK) in complex with a coenzyme A derivative, Form-I (LT)
Overview
Pantothenate kinase (PanK) is a ubiquitous and essential enzyme that catalyzes the first step of the universal coenzyme A biosynthetic pathway. In this step, pantothenate (vitamin B(5)) is converted to 4'-phosphopantothenate, which subsequently forms coenzyme A in four enzymatic steps. The complex of this enzyme from Mycobacterium tuberculosis (MtPanK) with a derivative of the feedback inhibitor coenzyme A has been crystallized in two forms and its structure solved. The structure was refined in both forms using room-temperature and low-temperature X-ray data. In both forms, the MtPanK subunit has a mononucleotide-binding fold with a seven-stranded central beta-sheet and helices on either side. However, there is a small though significant difference in subunit association between the two forms. The structure is also grossly similar to the enzyme from Escherichia coli. The active-site pocket and the dimeric interface are on two opposite sides of the PanK subunit. The enzymes from M. tuberculosis and E. coli exhibit several differences, particularly at the dimeric interface. On the other hand, the coenzyme A-binding region is almost entirely conserved. A delineation of the invariant and variable features of the PanK structure further indicates that the dimeric interface is very variable, while the coenzyme A-binding site is substantially invariant. A sequence alignment involving various bacterial PanKs is in agreement with this conclusion. The strong correlation between structural plasticity, evolutionary conservation and variability and function exhibited by the molecule could be important in the design of species-specific inhibitors of the enzyme.
About this Structure
2GET is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Pantothenate kinase, with EC number 2.7.1.33 Full crystallographic information is available from OCA.
Reference
Invariance and variability in bacterial PanK: a study based on the crystal structure of Mycobacterium tuberculosis PanK., Das S, Kumar P, Bhor V, Surolia A, Vijayan M, Acta Crystallogr D Biol Crystallogr. 2006 Jun;62(Pt 6):628-38. Epub 2006, May 12. PMID:16699190
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