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==Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) from Helicobacter pylori complexed with compound 1==
The line below this paragraph, containing "STRUCTURE_2glp", creates the "Structure Box" on the page.
<StructureSection load='2glp' size='340' side='right'caption='[[2glp]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2glp]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_SS1 Helicobacter pylori SS1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GLP FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BDE:N-[(1E)-(3,5-DIBROMO-2,4-DIHYDROXYPHENYL)METHYLENE]NICOTINOHYDRAZIDE'>BDE</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
{{STRUCTURE_2glp|  PDB=2glp  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2glp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2glp OCA], [https://pdbe.org/2glp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2glp RCSB], [https://www.ebi.ac.uk/pdbsum/2glp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2glp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABZ_HELPY FABZ_HELPY] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406]
== 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/gl/2glp_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=2glp ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
beta-Hydroxyacyl-acyl carrier protein dehydratase (FabZ) is an important enzyme for the elongation cycles of both saturated and unsaturated fatty acids biosyntheses in the type II fatty acid biosynthesis system (FAS II) pathway. FabZ has been an essential target for the discovery of compounds effective against pathogenic microbes. In this work, to characterize the catalytic and inhibitory mechanisms of FabZ, the crystal structures of the FabZ of Helicobacter pylori (HpFabZ) and its complexes with two newly discovered inhibitors have been solved. Different from the structures of other bacterial FabZs, HpFabZ contains an extra short two-turn alpha-helix (alpha4) between alpha3 and beta3, which plays an important role in shaping the substrate-binding tunnel. Residue Tyr-100 at the entrance of the tunnel adopts either an open or closed conformation in the crystal structure. The crystal structural characterization, the binding affinity determination, and the enzymatic activity assay of the HpFabZ mutant (Y100A) confirm the importance of Tyr-100 in catalytic activity and substrate binding. Residue Phe-83 at the exit tunnel was also refined in two alternative conformations, leading the tunnel to form an L-shape and U-shape. All these data thus contributed much to understanding the catalytic mechanism of HpFabZ. In addition, the co-crystal structures of HpFabZ with its inhibitors have suggested that the enzymatic activity of HpFabZ could be inhibited either by occupying the entrance of the tunnel or plugging the tunnel to prevent the substrate from accessing the active site. Our study has provided some insights into the catalytic and inhibitory mechanisms of FabZ, thus facilitating antibacterial agent development.


'''Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) from Helicobacter pylori complexed with compound 1'''
Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).,Zhang L, Liu W, Hu T, Du L, Luo C, Chen K, Shen X, Jiang H J Biol Chem. 2008 Feb 29;283(9):5370-9. Epub 2007 Dec 19. PMID:18093984<ref>PMID:18093984</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2glp" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
ss-hydroxyacyl-ACP dehydratase (FabZ) is an important enzyme for the elongation cycles of fatty acids biosyntheses in the type-II fatty acid biosynthesis system (FAS II) pathway. FabZ has been an essential target for the discovery of compounds effective against pathogenic microbes. In this work, to characterize the catalytic and inhibitory mechanisms of FabZ, the crystal structures of the FabZ of Helicobacter pylori (HpFabZ) and its complexes with two newly discovered inhibitors have been solved. Different from the structures of other bacterial FabZs, HpFabZ contains an extra short two-turn a-helix (a4), which plays an important role in shaping the substrate-binding tunnel. Residue Tyr100 at the entrance of the tunnel adopts either an open or closed conformation in the crystal structure. The crystal structural characterization, the binding affinity determination and the enzymatic activity assay of the HpFabZ mutant (Y100A) confirm the importance of Tyr100 in catalytic activity and substrate binding. Residue Phe83 at the exit tunnel was also refined in two alternative conformations, leading the tunnel to form L-shape and U-shape. All these data thus contributed a lot to understanding the catalytic mechanism of HpFabZ. In addition, the co-crystal structures of HpFabZ with its inhibitors have suggested that the enzymatic activity of HpFabZ could be inhibited either by occupying the entrance of the tunnel or plugging the tunnel to prevent the substrate from accessing the active site. Our study is expected to have provided some insights into the catalytic and inhibitory mechanisms of FabZ thus facilitating the antibacterial agent development.
*[[Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures|Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2GLP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GLP OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Helicobacter pylori SS1]]
Structural basis for catalytic and inhibitory mechanisms of beta -hydroxyacyl-acyl carrier protein dehydratase (FabZ)., Zhang L, Liu W, Hu T, Du L, Luo C, Chen K, Shen X, Jiang H, J Biol Chem. 2007 Dec 19;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18093984 18093984]
[[Category: Large Structures]]
[[Category: Helicobacter pylori]]
[[Category: Jiang H]]
[[Category: Single protein]]
[[Category: Liu W]]
[[Category: Jiang, H.]]
[[Category: Shen X]]
[[Category: Liu, W.]]
[[Category: Zhang L]]
[[Category: Shen, X.]]
[[Category: Zhang, L.]]
[[Category: Fabz complex]]
[[Category: Lyase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:14:55 2008''

Latest revision as of 11:49, 25 October 2023

Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) from Helicobacter pylori complexed with compound 1Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase(FabZ) from Helicobacter pylori complexed with compound 1

Structural highlights

2glp is a 6 chain structure with sequence from Helicobacter pylori SS1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.42Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FABZ_HELPY Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406]

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

beta-Hydroxyacyl-acyl carrier protein dehydratase (FabZ) is an important enzyme for the elongation cycles of both saturated and unsaturated fatty acids biosyntheses in the type II fatty acid biosynthesis system (FAS II) pathway. FabZ has been an essential target for the discovery of compounds effective against pathogenic microbes. In this work, to characterize the catalytic and inhibitory mechanisms of FabZ, the crystal structures of the FabZ of Helicobacter pylori (HpFabZ) and its complexes with two newly discovered inhibitors have been solved. Different from the structures of other bacterial FabZs, HpFabZ contains an extra short two-turn alpha-helix (alpha4) between alpha3 and beta3, which plays an important role in shaping the substrate-binding tunnel. Residue Tyr-100 at the entrance of the tunnel adopts either an open or closed conformation in the crystal structure. The crystal structural characterization, the binding affinity determination, and the enzymatic activity assay of the HpFabZ mutant (Y100A) confirm the importance of Tyr-100 in catalytic activity and substrate binding. Residue Phe-83 at the exit tunnel was also refined in two alternative conformations, leading the tunnel to form an L-shape and U-shape. All these data thus contributed much to understanding the catalytic mechanism of HpFabZ. In addition, the co-crystal structures of HpFabZ with its inhibitors have suggested that the enzymatic activity of HpFabZ could be inhibited either by occupying the entrance of the tunnel or plugging the tunnel to prevent the substrate from accessing the active site. Our study has provided some insights into the catalytic and inhibitory mechanisms of FabZ, thus facilitating antibacterial agent development.

Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).,Zhang L, Liu W, Hu T, Du L, Luo C, Chen K, Shen X, Jiang H J Biol Chem. 2008 Feb 29;283(9):5370-9. Epub 2007 Dec 19. PMID:18093984[1]

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

See Also

References

  1. ↑ Zhang L, Liu W, Hu T, Du L, Luo C, Chen K, Shen X, Jiang H. Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J Biol Chem. 2008 Feb 29;283(9):5370-9. Epub 2007 Dec 19. PMID:18093984 doi:10.1074/jbc.M705566200

2glp, resolution 2.42Å

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