4aox: Difference between revisions
New page: '''Unreleased structure''' The entry 4aox is ON HOLD until Paper Publication Authors: Franceschini, S., van Beek, H.L., Martinoli, C., Fraaije, M.W., Mattevi, A. Description: |
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==Oxidized steroid monooxygenase bound to NADP== | |||
<StructureSection load='4aox' size='340' side='right'caption='[[4aox]], [[Resolution|resolution]] 2.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aox]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodococcus_rhodochrous Rhodococcus rhodochrous]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AOX 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]] 2.42Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4aox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aox OCA], [https://pdbe.org/4aox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aox RCSB], [https://www.ebi.ac.uk/pdbsum/4aox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aox ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O50641_RHORH O50641_RHORH] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Steroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer-Villiger conversion of progesterone into progesterone acetate using FAD as prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence similarity with well-characterized Baeyer-Villiger monooxygenases, including phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative biochemical and structural analysis of STMO can be particularly insightful with regard to the understanding of the substrate-specificity properties of Baeyer-Villiger monooxygenases that are emerging as promising tools in biocatalytic applications and as targets for prodrug activation. The crystal structures of STMO in the native, NADP+-bound, and two mutant forms reveal structural details on this microbial steroid-degrading enzyme. The binding of the nicotinamide ring of NADP+ is shifted with respect to the flavin compared to that observed in other monooxygenases of the same class. This finding fully supports the idea that NADP(H) adopts various positions during the catalytic cycle to perform its multiple functions in catalysis. The active site closely resembles that of phenylacetone monooxygenase. This observation led us to discover that STMO is capable of acting also on phenylacetone, which implies an impressive level of substrate promiscuity. The investigation of six mutants that target residues on the surface of the substrate-binding site reveals that enzymatic conversions of both progesterone and phenylacetone are largely insensitive to relatively drastic amino acid changes, with some mutants even displaying enhanced activity on progesterone. These features possibly reflect the fact that these enzymes are continuously evolving to acquire new activities, depending on the emerging availabilities of new compounds in the living environment. | |||
Exploring the structural basis of substrate preferences in Baeyer-Villiger monooxygenases: insight from steroid monooxygenase.,Franceschini S, van Beek HL, Pennetta A, Martinoli C, Fraaije MW, Mattevi A J Biol Chem. 2012 May 17. PMID:22605340<ref>PMID:22605340</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4aox" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rhodococcus rhodochrous]] | |||
[[Category: Fraaije MW]] | |||
[[Category: Franceschini S]] | |||
[[Category: Martinoli C]] | |||
[[Category: Mattevi A]] | |||
[[Category: Van Beek HL]] | |||
Latest revision as of 14:32, 20 December 2023
Oxidized steroid monooxygenase bound to NADPOxidized steroid monooxygenase bound to NADP
Structural highlights
FunctionPublication Abstract from PubMedSteroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer-Villiger conversion of progesterone into progesterone acetate using FAD as prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence similarity with well-characterized Baeyer-Villiger monooxygenases, including phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative biochemical and structural analysis of STMO can be particularly insightful with regard to the understanding of the substrate-specificity properties of Baeyer-Villiger monooxygenases that are emerging as promising tools in biocatalytic applications and as targets for prodrug activation. The crystal structures of STMO in the native, NADP+-bound, and two mutant forms reveal structural details on this microbial steroid-degrading enzyme. The binding of the nicotinamide ring of NADP+ is shifted with respect to the flavin compared to that observed in other monooxygenases of the same class. This finding fully supports the idea that NADP(H) adopts various positions during the catalytic cycle to perform its multiple functions in catalysis. The active site closely resembles that of phenylacetone monooxygenase. This observation led us to discover that STMO is capable of acting also on phenylacetone, which implies an impressive level of substrate promiscuity. The investigation of six mutants that target residues on the surface of the substrate-binding site reveals that enzymatic conversions of both progesterone and phenylacetone are largely insensitive to relatively drastic amino acid changes, with some mutants even displaying enhanced activity on progesterone. These features possibly reflect the fact that these enzymes are continuously evolving to acquire new activities, depending on the emerging availabilities of new compounds in the living environment. Exploring the structural basis of substrate preferences in Baeyer-Villiger monooxygenases: insight from steroid monooxygenase.,Franceschini S, van Beek HL, Pennetta A, Martinoli C, Fraaije MW, Mattevi A J Biol Chem. 2012 May 17. PMID:22605340[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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