4aq2: Difference between revisions
No edit summary |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==resting state of homogentisate 1,2-dioxygenase== | ||
[[4aq2]] is a 12 chain structure with sequence from [ | <StructureSection load='4aq2' size='340' side='right'caption='[[4aq2]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aq2]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida_KT2440 Pseudomonas putida KT2440]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AQ2 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=4aq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aq2 OCA], [https://pdbe.org/4aq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aq2 RCSB], [https://www.ebi.ac.uk/pdbsum/4aq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aq2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HGD_PSEPK HGD_PSEPK] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Homogentisate 1,2-dioxygenase (HGDO) uses a mononuclear nonheme Fe2+ to catalyze the oxidative ring cleavage in the degradation of Tyr and Phe by producing maleylacetoacetate from homogentisate (2,5-dihydroxyphenylacetate). Here, we report three crystal structures of HGDO, revealing five different steps in its reaction cycle at 1.7-1.98 A resolution. The resting state structure displays an octahedral coordination for Fe2+ with two histidine residues (His331 and His367), a bidentate carboxylate ligand (Glu337), and two water molecules. Homogentisate binds as a monodentate ligand to Fe2+, and its interaction with Tyr346 invokes the folding of a loop over the active site, effectively shielding it from solvent. Binding of homogentisate is driven by enthalpy and is entropically disfavored as shown by anoxic isothermal titration calorimetry. Three different reaction cycle intermediates have been trapped in different HGDO subunits of a single crystal showing the influence of crystal packing interactions on the course of enzymatic reactions. The observed superoxo:semiquinone-, alkylperoxo-, and product-bound intermediates have been resolved in a crystal grown anoxically with homogentisate, which was subsequently incubated with dioxygen. We demonstrate that, despite different folds, active site architectures, and Fe2+ coordination, extradiol dioxygenases can proceed through the same principal reaction intermediates to catalyze the O2-dependent cleavage of aromatic rings. Thus, convergent evolution of nonhomologous enzymes using the 2-His-1-carboxylate facial triad motif developed different solutions to stabilize closely related intermediates in unlike environments. | |||
Visualizing the substrate-, superoxo-, alkylperoxo-, and product-bound states at the nonheme Fe(II) site of homogentisate dioxygenase.,Jeoung JH, Bommer M, Lin TY, Dobbek H Proc Natl Acad Sci U S A. 2013 Jul 15. PMID:23858455<ref>PMID:23858455</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4aq2" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Dioxygenase|Dioxygenase]] | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
[[Category: | </StructureSection> | ||
[[Category: Pseudomonas putida | [[Category: Large Structures]] | ||
[[Category: Bommer | [[Category: Pseudomonas putida KT2440]] | ||
[[Category: Dobbek | [[Category: Bommer M]] | ||
[[Category: Jeoung | [[Category: Dobbek H]] | ||
[[Category: Lin | [[Category: Jeoung J-H]] | ||
[[Category: Lin T-Y]] | |||
Latest revision as of 14:32, 20 December 2023
resting state of homogentisate 1,2-dioxygenaseresting state of homogentisate 1,2-dioxygenase
Structural highlights
FunctionPublication Abstract from PubMedHomogentisate 1,2-dioxygenase (HGDO) uses a mononuclear nonheme Fe2+ to catalyze the oxidative ring cleavage in the degradation of Tyr and Phe by producing maleylacetoacetate from homogentisate (2,5-dihydroxyphenylacetate). Here, we report three crystal structures of HGDO, revealing five different steps in its reaction cycle at 1.7-1.98 A resolution. The resting state structure displays an octahedral coordination for Fe2+ with two histidine residues (His331 and His367), a bidentate carboxylate ligand (Glu337), and two water molecules. Homogentisate binds as a monodentate ligand to Fe2+, and its interaction with Tyr346 invokes the folding of a loop over the active site, effectively shielding it from solvent. Binding of homogentisate is driven by enthalpy and is entropically disfavored as shown by anoxic isothermal titration calorimetry. Three different reaction cycle intermediates have been trapped in different HGDO subunits of a single crystal showing the influence of crystal packing interactions on the course of enzymatic reactions. The observed superoxo:semiquinone-, alkylperoxo-, and product-bound intermediates have been resolved in a crystal grown anoxically with homogentisate, which was subsequently incubated with dioxygen. We demonstrate that, despite different folds, active site architectures, and Fe2+ coordination, extradiol dioxygenases can proceed through the same principal reaction intermediates to catalyze the O2-dependent cleavage of aromatic rings. Thus, convergent evolution of nonhomologous enzymes using the 2-His-1-carboxylate facial triad motif developed different solutions to stabilize closely related intermediates in unlike environments. Visualizing the substrate-, superoxo-, alkylperoxo-, and product-bound states at the nonheme Fe(II) site of homogentisate dioxygenase.,Jeoung JH, Bommer M, Lin TY, Dobbek H Proc Natl Acad Sci U S A. 2013 Jul 15. PMID:23858455[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||