This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4icy

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:53, 1 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Tracing the Evolution of Angucyclinone Monooxygenases: Structural Determinants for C-12b Hydroxylation and Substrate Inhibition in PgaE==
==Tracing the Evolution of Angucyclinone Monooxygenases: Structural Determinants for C-12b Hydroxylation and Substrate Inhibition in PgaE==
-
<StructureSection load='4icy' size='340' side='right' caption='[[4icy]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+
<StructureSection load='4icy' size='340' side='right'caption='[[4icy]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4icy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_sp._pga64 Streptomyces sp. pga64]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ICY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ICY FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4icy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._PGA64 Streptomyces sp. PGA64]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ICY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ICY FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qa1|2qa1]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pgaE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=161235 Streptomyces sp. PGA64])</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=4icy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4icy OCA], [https://pdbe.org/4icy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4icy RCSB], [https://www.ebi.ac.uk/pdbsum/4icy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4icy ProSAT]</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=4icy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4icy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4icy RCSB], [http://www.ebi.ac.uk/pdbsum/4icy PDBsum]</span></td></tr>
+
</table>
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[https://www.uniprot.org/uniprot/Q93LY7_9ACTN Q93LY7_9ACTN]
-
Two functionally distinct homologous flavoprotein hydroxylases, PgaE and JadH, have been identified as branching points in the biosynthesis of the polyketide antibiotics gaudimycin C and jadomycin A, respectively. These evolutionarily related enzymes are both bifunctional and able to catalyze the same initial reaction, C-12 hydroxylation of the common angucyclinone intermediate prejadomycin. The enzymes diverge in their secondary activities, which include hydroxylation at C-12b by PgaE and dehydration at C-4a/C-12b by JadH. A further difference is that the C-12 hydroxylation is subject to substrate inhibition only in PgaE. Here we have identified regions associated with the C-12b hydroxylation in PgaE by extensive chimeragenesis, focusing on regions surrounding the active site. The results highlight the importance of a hairpin-beta motif near the dimer interface, with two nonconserved residues, P78 and I79 (corresponding to Q89 and F90, respectively, in JadH), and invariant residue H73 playing key roles. Kinetic characterization of PgaE variants demonstrates that the secondary C-12b hydroxylation and substrate inhibition by prejadomycin are likely to be interlinked. The crystal structure of the PgaE P78Q/I79F variant at 2.4 A resolution confirms that the changes do not alter the conformation of the beta-strand secondary structure and that the side chains of these residues in effect point away from the active site toward the dimer interface. The results support a catalytic model for PgaE containing two binding modes for C-12 and C-12b hydroxylations, where binding of prejadomycin in the orientation for C-12b hydroxylation leads to substrate inhibition. The presence of an allosteric network is evident based on enzyme kinetics.
+
-
 
+
-
Tracing the Evolution of Angucyclinone Monooxygenases: Structural Determinants for C-12b Hydroxylation and Substrate Inhibition in PgaE.,Kallio P, Patrikainen P, Belogurov GA, Mantsala P, Yang K, Niemi J, Metsa-Ketela M Biochemistry. 2013 Jul 2;52(26):4507-16. doi: 10.1021/bi400381s. Epub 2013 Jun, 17. PMID:23731237<ref>PMID:23731237</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Streptomyces sp. pga64]]
+
[[Category: Large Structures]]
-
[[Category: Belogurov, G]]
+
[[Category: Streptomyces sp. PGA64]]
-
[[Category: Kallio, P]]
+
[[Category: Belogurov G]]
-
[[Category: Mantsala, P]]
+
[[Category: Kallio P]]
-
[[Category: Metsa-Ketela, M]]
+
[[Category: Mantsala P]]
-
[[Category: Niemi, J]]
+
[[Category: Metsa-Ketela M]]
-
[[Category: Patrikainen, P]]
+
[[Category: Niemi J]]
-
[[Category: Yang, K]]
+
[[Category: Patrikainen P]]
-
[[Category: Fad]]
+
[[Category: Yang K]]
-
[[Category: Fad-dependent aromatic hydroxylation]]
+
-
[[Category: Monooxygenase]]
+
-
[[Category: Oxidoreductase]]
+

Current revision

Tracing the Evolution of Angucyclinone Monooxygenases: Structural Determinants for C-12b Hydroxylation and Substrate Inhibition in PgaE

PDB ID 4icy

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4icy"
Personal tools