1qzf: Difference between revisions

Revision as of 15:45, 21 February 2008

Crystal structure of DHFR-TS from Cryptosporidium hominis

OverviewOverview

We have determined the crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that has extensive interactions with the opposite DHFR-TS monomer of the homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis and of previously solved structures of DHFR-TS from Plasmodium falciparum and Leishmania major reveals that the linker domain primarily controls the relative orientation of the DHFR and TS domains. Using the tertiary structure of the linker domains, we have been able to place a number of protozoa in two distinct and dissimilar structural families corresponding to two evolutionary families and provide the first structural evidence validating the use of DHFR-TS as a tool of phylogenetic classification. Furthermore, the structure of C. hominis DHFR-TS calls into question surface electrostatic channeling as the universal means of dihydrofolate transport between TS and DHFR in the bifunctional enzyme.

About this StructureAbout this Structure

1QZF is a Single protein structure of sequence from Cryptosporidium hominis with , , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase., O'Neil RH, Lilien RH, Donald BR, Stroud RM, Anderson AC, J Biol Chem. 2003 Dec 26;278(52):52980-7. Epub 2003 Oct 9. PMID:14555647

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OCA

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-[[Image:1qzf.gif|left|200px]]<br /><applet load="1qzf" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1qzf.gif|left|200px]]<br /><applet load="1qzf" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1qzf, resolution 2.80&Aring;" />
 '''Crystal structure of DHFR-TS from Cryptosporidium hominis'''<br />
 ==Overview==
-We have determined the crystal structure of dihydrofolate, reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that, has extensive interactions with the opposite DHFR-TS monomer of the, homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis, and of previously solved structures of DHFR-TS from Plasmodium falciparum, and Leishmania major reveals that the linker domain primarily controls the, relative orientation of the DHFR and TS domains. Using the tertiary, structure of the linker domains, we have been able to place a number of, protozoa in two distinct and dissimilar structural families corresponding, to two evolutionary families and provide the first structural evidence, validating the use of DHFR-TS as a tool of phylogenetic classification., Furthermore, the structure of C. hominis DHFR-TS calls into question, surface electrostatic channeling as the universal means of dihydrofolate, transport between TS and DHFR in the bifunctional enzyme.
+We have determined the crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that has extensive interactions with the opposite DHFR-TS monomer of the homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis and of previously solved structures of DHFR-TS from Plasmodium falciparum and Leishmania major reveals that the linker domain primarily controls the relative orientation of the DHFR and TS domains. Using the tertiary structure of the linker domains, we have been able to place a number of protozoa in two distinct and dissimilar structural families corresponding to two evolutionary families and provide the first structural evidence validating the use of DHFR-TS as a tool of phylogenetic classification. Furthermore, the structure of C. hominis DHFR-TS calls into question surface electrostatic channeling as the universal means of dihydrofolate transport between TS and DHFR in the bifunctional enzyme.
 ==About this Structure==
-QZF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis] with UMP, CB3, FOL and NDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QZF OCA].
+QZF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis] with <scene name='pdbligand=UMP:'>UMP</scene>, <scene name='pdbligand=CB3:'>CB3</scene>, <scene name='pdbligand=FOL:'>FOL</scene> and <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QZF OCA].
 ==Reference==
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 [[Category: Cryptosporidium hominis]]
 [[Category: Single protein]]
-[[Category: Anderson, A.C.]]
+[[Category: Anderson, A C.]]
-[[Category: Donald, B.R.]]
+[[Category: Donald, B R.]]
-[[Category: Lilien, R.H.]]
+[[Category: Lilien, R H.]]
-[[Category: Neil, R.H.O.]]
+[[Category: Neil, R H.O.]]
-[[Category: Stroud, R.M.]]
+[[Category: Stroud, R M.]]
 [[Category: CB3]]
 [[Category: FOL]]
@@ Line 24: / Line 24: @@
 [[Category: bifunctional enzyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 21:50:56 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:45:24 2008''