1tx0: Difference between revisions

Revision as of 16:18, 21 February 2008

Dihydropteroate Synthetase, With Bound Product Analogue Pteroic Acid, From Bacillus anthracis

OverviewOverview

Dihydropterate synthase (DHPS) is the target for the sulfonamide class of antibiotics, but increasing resistance has encouraged the development of new therapeutic agents against this enzyme. One approach is to identify molecules that occupy the pterin binding pocket which is distinct from the pABA binding pocket that binds sulfonamides. Toward this goal, we present five crystal structures of DHPS from Bacillus anthracis, a well-documented bioterrorism agent. Three DHPS structures are already known, but our B. anthracis structures provide new insights into the enzyme mechanism. We show how an arginine side chain mimics the pterin ring in binding within the pterin binding pocket. The structures of two substrate analog complexes and the first structure of a DHPS-product complex offer new insights into the catalytic mechanism and the architecture of the pABA binding pocket. Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine.

About this StructureAbout this Structure

1TX0 is a Single protein structure of sequence from Bacillus anthracis str. a2012 with and as ligands. Active as Dihydropteroate synthase, with EC number 2.5.1.15 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of 7,8-dihydropteroate synthase from Bacillus anthracis: mechanism and novel inhibitor design., Babaoglu K, Qi J, Lee RE, White SW, Structure. 2004 Sep;12(9):1705-17. PMID:15341734

Page seeded by OCA on Thu Feb 21 15:18:13 2008

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OCA

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-[[Image:1tx0.jpg|left|200px]]<br /><applet load="1tx0" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tx0.jpg|left|200px]]<br /><applet load="1tx0" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tx0, resolution 2.15&Aring;" />
 '''Dihydropteroate Synthetase, With Bound Product Analogue Pteroic Acid, From Bacillus anthracis'''<br />
 ==Overview==
-Dihydropterate synthase (DHPS) is the target for the sulfonamide class of, antibiotics, but increasing resistance has encouraged the development of, new therapeutic agents against this enzyme. One approach is to identify, molecules that occupy the pterin binding pocket which is distinct from the, pABA binding pocket that binds sulfonamides. Toward this goal, we present, five crystal structures of DHPS from Bacillus anthracis, a well-documented, bioterrorism agent. Three DHPS structures are already known, but our B., anthracis structures provide new insights into the enzyme mechanism. We, show how an arginine side chain mimics the pterin ring in binding within, the pterin binding pocket. The structures of two substrate analog, complexes and the first structure of a DHPS-product complex offer new, insights into the catalytic mechanism and the architecture of the pABA, binding pocket. Finally, as an initial step in the development of, pterin-based inhibitors, we present the structure of DHPS complexed with, 5-nitro-6-methylamino-isocytosine.
+Dihydropterate synthase (DHPS) is the target for the sulfonamide class of antibiotics, but increasing resistance has encouraged the development of new therapeutic agents against this enzyme. One approach is to identify molecules that occupy the pterin binding pocket which is distinct from the pABA binding pocket that binds sulfonamides. Toward this goal, we present five crystal structures of DHPS from Bacillus anthracis, a well-documented bioterrorism agent. Three DHPS structures are already known, but our B. anthracis structures provide new insights into the enzyme mechanism. We show how an arginine side chain mimics the pterin ring in binding within the pterin binding pocket. The structures of two substrate analog complexes and the first structure of a DHPS-product complex offer new insights into the catalytic mechanism and the architecture of the pABA binding pocket. Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine.
 ==About this Structure==
-TX0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_str._a2012 Bacillus anthracis str. a2012] with SO4 and PT1 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydropteroate_synthase Dihydropteroate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.15 2.5.1.15] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TX0 OCA].
+TX0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_str._a2012 Bacillus anthracis str. a2012] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=PT1:'>PT1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydropteroate_synthase Dihydropteroate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.15 2.5.1.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TX0 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Babaoglu, K.]]
-[[Category: Lee, R.E.]]
+[[Category: Lee, R E.]]
 [[Category: Qi, J.]]
-[[Category: White, S.W.]]
+[[Category: White, S W.]]
 [[Category: PT1]]
 [[Category: SO4]]
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 [[Category: pterine]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:54:02 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:13 2008''