1xfc
From Proteopedia
(New page: 200px<br /><applet load="1xfc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xfc, resolution 1.90Å" /> '''The 1.9 A crystal st...) |
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| - | [[Image:1xfc.gif|left|200px]]<br /><applet load="1xfc" size=" | + | [[Image:1xfc.gif|left|200px]]<br /><applet load="1xfc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xfc, resolution 1.90Å" /> | caption="1xfc, resolution 1.90Å" /> | ||
'''The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site'''<br /> | '''The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We report the crystal structure of alanine racemase from Mycobacterium | + | We report the crystal structure of alanine racemase from Mycobacterium tuberculosis (Alr(Mtb)) at 1.9 A resolution. In our structure, Alr(Mtb) is found to be a dimer formed by two crystallographically different monomers, each comprising 384 residues. The domain makeup of each monomer is similar to that of Bacillus and Pseudomonas alanine racemases and includes both an alpha/beta-barrel at the N-terminus and a C-terminus primarily made of beta-strands. The hinge angle between these two domains is unique for Alr(Mtb), but the active site geometry is conserved. In Alr(Mtb), the PLP cofactor is covalently bound to the protein via an internal aldimine bond with Lys42. No guest substrate is noted in its active site, although some residual electron density is observed in the enzyme's active site pocket. Analysis of the active site pocket, in the context of other known alanine racemases, allows us to propose the inclusion of conserved residues found at the entrance to the binding pocket as additional targets in ongoing structure-aided drug design efforts. Also, as observed in other alanine racemase structures, PLP adopts a conformation that significantly distorts the planarity of the extended conjugated system between the PLP ring and the internal aldimine bond. |
==About this Structure== | ==About this Structure== | ||
| - | 1XFC 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 PLP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Full crystallographic information is available from [http:// | + | 1XFC 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=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XFC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Benedik, M | + | [[Category: Benedik, M J.]] |
| - | [[Category: Briggs, J | + | [[Category: Briggs, J M.]] |
[[Category: Ebalunode, J.]] | [[Category: Ebalunode, J.]] | ||
[[Category: Im, H.]] | [[Category: Im, H.]] | ||
[[Category: Kohn, H.]] | [[Category: Kohn, H.]] | ||
| - | [[Category: Krause, K | + | [[Category: Krause, K L.]] |
[[Category: LeMagueres, P.]] | [[Category: LeMagueres, P.]] | ||
[[Category: Strych, U.]] | [[Category: Strych, U.]] | ||
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[[Category: internal aldimine form]] | [[Category: internal aldimine form]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:10 2008'' |
Revision as of 13:54, 21 February 2008
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The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site
Overview
We report the crystal structure of alanine racemase from Mycobacterium tuberculosis (Alr(Mtb)) at 1.9 A resolution. In our structure, Alr(Mtb) is found to be a dimer formed by two crystallographically different monomers, each comprising 384 residues. The domain makeup of each monomer is similar to that of Bacillus and Pseudomonas alanine racemases and includes both an alpha/beta-barrel at the N-terminus and a C-terminus primarily made of beta-strands. The hinge angle between these two domains is unique for Alr(Mtb), but the active site geometry is conserved. In Alr(Mtb), the PLP cofactor is covalently bound to the protein via an internal aldimine bond with Lys42. No guest substrate is noted in its active site, although some residual electron density is observed in the enzyme's active site pocket. Analysis of the active site pocket, in the context of other known alanine racemases, allows us to propose the inclusion of conserved residues found at the entrance to the binding pocket as additional targets in ongoing structure-aided drug design efforts. Also, as observed in other alanine racemase structures, PLP adopts a conformation that significantly distorts the planarity of the extended conjugated system between the PLP ring and the internal aldimine bond.
About this Structure
1XFC is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Active as Alanine racemase, with EC number 5.1.1.1 Full crystallographic information is available from OCA.
Reference
The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site., LeMagueres P, Im H, Ebalunode J, Strych U, Benedik MJ, Briggs JM, Kohn H, Krause KL, Biochemistry. 2005 Feb 8;44(5):1471-81. PMID:15683232
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