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1eye

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Revision as of 04:01, 6 September 2017

1.7 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF 6-HYDROXYMETHYL-7,8-DIHYDROPTEROATE SYNTHASE (DHPS) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH 6-HYDROXYMETHYLPTERIN MONOPHOSPHATE

Structural highlights

1eye is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1aj0, 1ajz, 1aj2, 1ad1, 1ad4
Activity:	Dihydropteroate synthase, with EC number 2.5.1.15
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The enzyme 7,8-dihydropteroate synthase (DHPS) catalyzes the condensation of para-aminobenzoic acid (pABA) with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to form 7,8-dihydropteroate and pyrophosphate. DHPS is essential for the de novo synthesis of folate in prokaryotes, lower eukaryotes, and in plants, but is absent in mammals. Inhibition of this enzyme's activity by sulfonamide and sulfone drugs depletes the folate pool, resulting in growth inhibition and cell death. Here, we report the 1.7 A resolution crystal structure of the binary complex of 6-hydroxymethylpterin monophosphate (PtP) with DHPS from Mycobacterium tuberculosis (Mtb), a pathogen responsible for the death of millions of human beings each year. Comparison to other DHPS structures reveals that the M. tuberculosis DHPS structure is in a unique conformation in which loop 1 closes over the active site. The Mtb DHPS structure hints at a mechanism in which both loops 1 and 2 play important roles in catalysis by shielding the active site from bulk solvent and allowing pyrophosphoryl transfer to occur. A binding mode for pABA, sulfonamides and sulfones is suggested based on: (i) the new conformation of the closed loop 1; (ii) the distribution of dapsone and sulfonamide resistance mutations; (iii) the observed direction of the bond between the 6-methyl carbon atom and the bridging oxygen atom to the alpha-phosphate group in the Mtb DHPS:PtP binary complex; and (iv) the conformation of loop 2 in the Escherichia coli DHPS structure. Finally, the Mtb DHPS structure reveals a highly conserved pterin binding pocket that may be exploited for the design of novel antimycobacterial agents.

Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action.,Baca AM, Sirawaraporn R, Turley S, Sirawaraporn W, Hol WG J Mol Biol. 2000 Oct 6;302(5):1193-212. PMID:11007651^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Baca AM, Sirawaraporn R, Turley S, Sirawaraporn W, Hol WG. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J Mol Biol. 2000 Oct 6;302(5):1193-212. PMID:11007651 doi:10.1006/jmbi.2000.4094

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1eye"

@@ Line 1: / Line 1: @@
 ==1.7 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF 6-HYDROXYMETHYL-7,8-DIHYDROPTEROATE SYNTHASE (DHPS) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH 6-HYDROXYMETHYLPTERIN MONOPHOSPHATE==
 <StructureSection load='1eye' size='340' side='right' caption='[[1eye]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1eye]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EYE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1eye]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EYE FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PMM:PTERIN-6-YL-METHYL-MONOPHOSPHATE'>PMM</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aj0|1aj0]], [[1ajz|1ajz]], [[1aj2|1aj2]], [[1ad1|1ad1]], [[1ad4|1ad4]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eye OCA], [http://pdbe.org/1eye PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1eye RCSB], [http://www.ebi.ac.uk/pdbsum/1eye PDBsum], [http://www.topsan.org/Proteins/TBSGC/1eye TOPSAN]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eye OCA], [http://pdbe.org/1eye PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1eye RCSB], [http://www.ebi.ac.uk/pdbsum/1eye PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1eye ProSAT], [http://www.topsan.org/Proteins/TBSGC/1eye TOPSAN]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1eye ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 35: / Line 36: @@
 </StructureSection>
 [[Category: Dihydropteroate synthase]]
-[[Category: Myctu]]
 [[Category: Baca, A M]]
 [[Category: Hol, W G.J]]

1eye

From Proteopedia

Revision as of 04:01, 6 September 2017

1.7 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF 6-HYDROXYMETHYL-7,8-DIHYDROPTEROATE SYNTHASE (DHPS) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH 6-HYDROXYMETHYLPTERIN MONOPHOSPHATE

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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