8dsn - Revision history

OCA at 07:10, 21 November 2024

2024-11-21T07:10:23Z

← Older revision		Revision as of 07:10, 21 November 2024
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	Peptidylglycine monooxygenase (PHM) is essential for the biosynthesis of many neuroendocrine peptides via a copper-dependent hydroxylation of a glycine-extended pro-peptide. The "canonical" mechanism requires the transfer of two electrons from one mononuclear copper (CuH, H-site) to a second mononuclear copper (CuM, M-site) which is the site of oxygen binding and catalysis. In most crystal structures the copper centers are separated by 11 A of disordered solvent, but recent work has established that a PHM variant H108A forms a closed conformer in the presence of citrate with a reduced Cu-Cu site separation of ~4 A. Here we report three new PHM structures where the H and M sites are separated by a longer distance of ~14 A. Variation in Cu-Cu distance is the result of a rotation of the M subdomain about a hinge point centered on the pro(199) -leu(200) -ile(201) triad which forms the linker between subdomains. The energetic cost of domain dynamics is likely small enough to allow free rotation of the subdomains relative to each other, adding credence to recent suggestions that an open-to-closed transition to form a binuclear oxygen binding intermediate is an essential element of catalysis. This inference would explain many experimental observations that are inconsistent with the current canonical mechanism including substrate-induced oxygen activation and isotope scrambling during the peroxide shunt~~. This article is protected by copyright. All rights reserved~~.		Peptidylglycine monooxygenase (PHM) is essential for the biosynthesis of many neuroendocrine peptides via a copper-dependent hydroxylation of a glycine-extended pro-peptide. The "canonical" mechanism requires the transfer of two electrons from one mononuclear copper (CuH, H-site) to a second mononuclear copper (CuM, M-site) which is the site of oxygen binding and catalysis. In most crystal structures the copper centers are separated by 11 A of disordered solvent, but recent work has established that a PHM variant H108A forms a closed conformer in the presence of citrate with a reduced Cu-Cu site separation of ~4 A. Here we report three new PHM structures where the H and M sites are separated by a longer distance of ~14 A. Variation in Cu-Cu distance is the result of a rotation of the M subdomain about a hinge point centered on the pro(199) -leu(200) -ile(201) triad which forms the linker between subdomains. The energetic cost of domain dynamics is likely small enough to allow free rotation of the subdomains relative to each other, adding credence to recent suggestions that an open-to-closed transition to form a binuclear oxygen binding intermediate is an essential element of catalysis. This inference would explain many experimental observations that are inconsistent with the current canonical mechanism including substrate-induced oxygen activation and isotope scrambling during the peroxide shunt.

	New ~~Structures Reveal Flexible Dynamics~~ between the ~~Subdomains~~ of ~~Peptidylglycine Monooxygenase~~. Implications for an ~~Open~~ to ~~Closed Mechanism~~.,Arias RJ, Welch EF, Blackburn NJ Protein Sci. 2023 ~~Mar 7~~:e4615. doi: 10.1002/pro.4615. PMID:36880254<ref>PMID:36880254</ref>		New structures reveal flexible dynamics between the subdomains of peptidylglycine monooxygenase. Implications for an open to closed mechanism.,Arias RJ, Welch EF, Blackburn NJ Protein Sci. 2023 Apr;32(4):e4615. doi: 10.1002/pro.4615. PMID:36880254<ref>PMID:36880254</ref>

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

OCA at 10:14, 25 October 2023

2023-10-25T10:14:01Z

← Older revision		Revision as of 10:14, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dsn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DSN FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dsn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DSN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.8Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8dsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dsn OCA], [https://pdbe.org/8dsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dsn RCSB], [https://www.ebi.ac.uk/pdbsum/8dsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dsn ProSAT]</span></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=8dsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dsn OCA], [https://pdbe.org/8dsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dsn RCSB], [https://www.ebi.ac.uk/pdbsum/8dsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dsn ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:23, 22 March 2023

2023-03-22T07:23:59Z

← Older revision		Revision as of 07:23, 22 March 2023
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	~~'''Unreleased structure'''~~

	The ~~entry 8dsn~~ is ~~ON HOLD until Paper~~ Publication		==Peptidylglycine alpha hydroxylating monoxygenase, Q272A==
			<StructureSection load='8dsn' size='340' side='right'caption='[[8dsn]], [[Resolution\|resolution]] 2.80Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8dsn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DSN FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8dsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dsn OCA], [https://pdbe.org/8dsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dsn RCSB], [https://www.ebi.ac.uk/pdbsum/8dsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dsn ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/AMD_RAT AMD_RAT] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Peptidylglycine monooxygenase (PHM) is essential for the biosynthesis of many neuroendocrine peptides via a copper-dependent hydroxylation of a glycine-extended pro-peptide. The "canonical" mechanism requires the transfer of two electrons from one mononuclear copper (CuH, H-site) to a second mononuclear copper (CuM, M-site) which is the site of oxygen binding and catalysis. In most crystal structures the copper centers are separated by 11 A of disordered solvent, but recent work has established that a PHM variant H108A forms a closed conformer in the presence of citrate with a reduced Cu-Cu site separation of ~4 A. Here we report three new PHM structures where the H and M sites are separated by a longer distance of ~14 A. Variation in Cu-Cu distance is the result of a rotation of the M subdomain about a hinge point centered on the pro(199) -leu(200) -ile(201) triad which forms the linker between subdomains. The energetic cost of domain dynamics is likely small enough to allow free rotation of the subdomains relative to each other, adding credence to recent suggestions that an open-to-closed transition to form a binuclear oxygen binding intermediate is an essential element of catalysis. This inference would explain many experimental observations that are inconsistent with the current canonical mechanism including substrate-induced oxygen activation and isotope scrambling during the peroxide shunt. This article is protected by copyright. All rights reserved.

	~~Authors:~~ Arias, R.J.~~, Blackburn, N~~.J.		New Structures Reveal Flexible Dynamics between the Subdomains of Peptidylglycine Monooxygenase. Implications for an Open to Closed Mechanism.,Arias RJ, Welch EF, Blackburn NJ Protein Sci. 2023 Mar 7:e4615. doi: 10.1002/pro.4615. PMID:36880254<ref>PMID:36880254</ref>

	~~Description~~: ~~Peptidylglycine alpha hydroxylating monoxygenase, Q272A~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: Arias~~, R.J~~]]		<div class="pdbe-citations 8dsn" style="background-color:#fffaf0;"></div>
	[[Category: Blackburn~~, N.J~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Rattus norvegicus]]
			[[Category: Arias RJ]]
			[[Category: Blackburn NJ]]

OCA at 05:31, 31 August 2022

2022-08-31T05:31:29Z

← Older revision		Revision as of 05:31, 31 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8dsn is ON HOLD		The entry 8dsn is ON HOLD until Paper Publication

	Authors: Arias, R.J., Blackburn, N.J.		Authors: Arias, R.J., Blackburn, N.J.

OCA: Protected "8dsn" [edit=sysop:move=sysop]

2022-08-03T03:55:20Z

Protected "8dsn" [edit=sysop:move=sysop]

← Older revision	Revision as of 03:55, 3 August 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8dsn is ON HOLD Authors: Arias, R.J., Blackburn, N.J. Description: Peptidylglycine alpha hydroxylating monoxygenase, Q272A [[Category: Unreleased S...

2022-08-03T03:55:19Z

New page: '''Unreleased structure''' The entry 8dsn is ON HOLD Authors: Arias, R.J., Blackburn, N.J. Description: Peptidylglycine alpha hydroxylating monoxygenase, Q272A [[Category: Unreleased S...

New page

'''Unreleased structure'''

The entry 8dsn is ON HOLD

Authors: Arias, R.J., Blackburn, N.J.

Description: Peptidylglycine alpha hydroxylating monoxygenase, Q272A
[[Category: Unreleased Structures]]
[[Category: Arias, R.J]]
[[Category: Blackburn, N.J]]