2vef: Difference between revisions
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New page: left|200px {{Structure |PDB= 2vef |SIZE=350|CAPTION= <scene name='initialview01'>2vef</scene>, resolution 1.80Å |SITE= <scene name='pdbsite=AC1:Po4+Binding+Site+... |
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==Dihydropteroate synthase from Streptococcus pneumoniae== | |||
<StructureSection load='2vef' size='340' side='right'caption='[[2vef]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2vef]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VEF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vef OCA], [https://pdbe.org/2vef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vef RCSB], [https://www.ebi.ac.uk/pdbsum/2vef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vef ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DHPS_STRR6 DHPS_STRR6] DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2vef_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<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/main_output.php?pdb_ID=2vef ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DHPS (dihydropteroate synthase) catalyses an essential step in the biosynthesis of folic acid and is the target for the sulfonamide group of antimicrobial drugs. In the present paper we report two crystal structures of DHPS from the respiratory pathogen Streptococcus pneumoniae: the apoenzyme at 1.8 A (1 A=0.1 nm) resolution and a complex with DHPP (6-hydroxymethyl-7,8-dihydropterin monophosphate) at 2.4 A resolution. The enzyme forms a alpha/beta barrel structure, with a highly conserved binding pocket for recognition of the pterin substrate, DHPPP (6-hydroxymethyl-7,8-dihydropterin pyrophosphate). There is a fixed order of substrate binding: DHPPP binds first, followed by the second substrate, pABA (p-aminobenzoic acid). Binding of PP(i) also allows the enzyme to recognize pABA or sulfonamide drugs, which act as pABA analogues. Using equilibrium and pre-steady state kinetic fluorescence measurements, we show that the on-rate for DHPPP binding to the enzyme is relatively low (2.6x10(5) M(-1) x s(-1)) and propose that binding of this substrate induces a large scale movement of the second loop in the enzyme structure to participate in the formation of the pABA-binding site. Two mutations which confer resistance to sulfonamide drugs do not affect DHPPP binding, but have a substantial effect on pABA and sulfonamide recognition. The results show that binding of DHPPP and pABA are separate distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process. | |||
Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance.,Levy C, Minnis D, Derrick JP Biochem J. 2008 Jun 1;412(2):379-88. PMID:18321242<ref>PMID:18321242</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vef" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
Dihydropteroate synthase | *[[Dihydropteroate synthase 3D structures|Dihydropteroate synthase 3D structures]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: | |||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
[[Category: Derrick | [[Category: Derrick JP]] | ||
[[Category: Levy | [[Category: Levy C]] | ||
Latest revision as of 12:58, 9 May 2024
Dihydropteroate synthase from Streptococcus pneumoniaeDihydropteroate synthase from Streptococcus pneumoniae
Structural highlights
FunctionDHPS_STRR6 DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide. 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 PubMedDHPS (dihydropteroate synthase) catalyses an essential step in the biosynthesis of folic acid and is the target for the sulfonamide group of antimicrobial drugs. In the present paper we report two crystal structures of DHPS from the respiratory pathogen Streptococcus pneumoniae: the apoenzyme at 1.8 A (1 A=0.1 nm) resolution and a complex with DHPP (6-hydroxymethyl-7,8-dihydropterin monophosphate) at 2.4 A resolution. The enzyme forms a alpha/beta barrel structure, with a highly conserved binding pocket for recognition of the pterin substrate, DHPPP (6-hydroxymethyl-7,8-dihydropterin pyrophosphate). There is a fixed order of substrate binding: DHPPP binds first, followed by the second substrate, pABA (p-aminobenzoic acid). Binding of PP(i) also allows the enzyme to recognize pABA or sulfonamide drugs, which act as pABA analogues. Using equilibrium and pre-steady state kinetic fluorescence measurements, we show that the on-rate for DHPPP binding to the enzyme is relatively low (2.6x10(5) M(-1) x s(-1)) and propose that binding of this substrate induces a large scale movement of the second loop in the enzyme structure to participate in the formation of the pABA-binding site. Two mutations which confer resistance to sulfonamide drugs do not affect DHPPP binding, but have a substantial effect on pABA and sulfonamide recognition. The results show that binding of DHPPP and pABA are separate distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process. Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance.,Levy C, Minnis D, Derrick JP Biochem J. 2008 Jun 1;412(2):379-88. PMID:18321242[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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