1sr9
From Proteopedia
(New page: 200px<br /><applet load="1sr9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sr9, resolution 2.0Å" /> '''Crystal Structure of ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1sr9.gif|left|200px]]<br /><applet load="1sr9" size=" | + | [[Image:1sr9.gif|left|200px]]<br /><applet load="1sr9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sr9, resolution 2.0Å" /> | caption="1sr9, resolution 2.0Å" /> | ||
'''Crystal Structure of LeuA from Mycobacterium tuberculosis'''<br /> | '''Crystal Structure of LeuA from Mycobacterium tuberculosis'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The leucine biosynthetic pathway is essential for the growth of | + | The leucine biosynthetic pathway is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes the first committed step in this pathway, has been determined by multiwavelength anomalous dispersion methods and refined at 2.0-A resolution in complex with its substrate alpha-ketoisovalerate. The structure reveals a tightly associated, domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM barrel catalytic domain, a helical linker domain, and a regulatory domain of novel fold. Mutational and crystallographic data indicate the latter as the site for leucine feedback inhibition of activity. Domain swapping enables the linker domain of one monomer to sit over the catalytic domain of the other, inserting residues into the active site that may be important in catalysis. The alpha-ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity that can accommodate acetyl-CoA. Sequence and structural similarities point to a catalytic mechanism similar to that of malate synthase and an evolutionary relationship with an aldolase that catalyzes the reverse reaction on a similar substrate. |
==About this Structure== | ==About this Structure== | ||
| - | 1SR9 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 ZN, CL and KIV as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] Full crystallographic information is available from [http:// | + | 1SR9 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=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=KIV:'>KIV</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SR9 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baker, E | + | [[Category: Baker, E N.]] |
[[Category: Koon, N.]] | [[Category: Koon, N.]] | ||
| - | [[Category: Squire, C | + | [[Category: Squire, C J.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: KIV]] | [[Category: KIV]] | ||
| Line 22: | Line 22: | ||
[[Category: tim barrel]] | [[Category: tim barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:04:24 2008'' |
Revision as of 13:04, 21 February 2008
|
Crystal Structure of LeuA from Mycobacterium tuberculosis
Overview
The leucine biosynthetic pathway is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes the first committed step in this pathway, has been determined by multiwavelength anomalous dispersion methods and refined at 2.0-A resolution in complex with its substrate alpha-ketoisovalerate. The structure reveals a tightly associated, domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM barrel catalytic domain, a helical linker domain, and a regulatory domain of novel fold. Mutational and crystallographic data indicate the latter as the site for leucine feedback inhibition of activity. Domain swapping enables the linker domain of one monomer to sit over the catalytic domain of the other, inserting residues into the active site that may be important in catalysis. The alpha-ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity that can accommodate acetyl-CoA. Sequence and structural similarities point to a catalytic mechanism similar to that of malate synthase and an evolutionary relationship with an aldolase that catalyzes the reverse reaction on a similar substrate.
About this Structure
1SR9 is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Active as 2-isopropylmalate synthase, with EC number 2.3.3.13 Full crystallographic information is available from OCA.
Reference
Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis., Koon N, Squire CJ, Baker EN, Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8295-300. Epub 2004 May 24. PMID:15159544
Page seeded by OCA on Thu Feb 21 15:04:24 2008
