6xai - Revision history

OCA at 07:10, 3 April 2024

OCA — Wed, 03 Apr 2024 07:10:54 GMT

←Older revision		Revision as of 07:10, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='6xai' size='340' side='right'caption='[[6xai]], [[Resolution\|resolution]] 1.49Å' scene=''>		<StructureSection load='6xai' size='340' side='right'caption='[[6xai]], [[Resolution\|resolution]] 1.49Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6xai]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp.~~_nrrl_f~~-5053 Streptomyces sp. ~~nrrl f~~-5053]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xai]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._NRRL_F-5053 Streptomyces sp. NRRL F-5053]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QRP:(3S,8AS)-3-(1H-INDOL-3-YLMETHYL)HEXAHYDROPYRROLO[1,2-A]PYRAZINE-1,4-DIONE'>QRP~~</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]] 1.489Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO~~</scene></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QRP:(3S,8AS)-3-(1H-INDOL-3-YLMETHYL)HEXAHYDROPYRROLO[1,2-A]PYRAZINE-1,4-DIONE'>QRP</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai 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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr>
	</table>		</table>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The dimeric diketopiperazine (DKPs) alkaloids are a diverse family of natural products (NPs) whose unique structural architectures and biological activities have inspired the development of new synthetic methodologies to access these molecules. However, catalyst-controlled methods that enable the selective formation of constitutional and stereoisomeric dimers from a single monomer are lacking. To resolve this long-standing synthetic challenge, we sought to characterize the biosynthetic enzymes that assemble these NPs for application in biocatalytic syntheses. Genome mining enabled identification of the cytochrome P450, NzeB (Streptomyces sp. NRRL F-5053), which catalyzes both intermolecular carbon-carbon (C-C) and carbon-nitrogen (C-N) bond formation. To identify the molecular basis for the flexible site-selectivity, stereoselectivity, and chemoselectivity of NzeB, we obtained high-resolution crystal structures (1.5 A) of the protein in complex with native and non-native substrates. This, to our knowledge, represents the first crystal structure of an oxidase catalyzing direct, intermolecular C-H amination. Site-directed mutagenesis was utilized to assess the role individual active-site residues play in guiding selective DKP dimerization. Finally, computational approaches were employed to evaluate plausible mechanisms regarding NzeB function and its ability to catalyze both C-C and C-N bond formation. These results provide a structural and computational rationale for the catalytic versatility of NzeB, as well as new insights into variables that control selectivity of CYP450 diketopiperazine dimerases.
-
-	Structure and Function of NzeB, a Versatile C-C and C-N Bond-Forming Diketopiperazine Dimerase.,Shende VV, Khatri Y, Newmister SA, Sanders JN, Lindovska P, Yu F, Doyon TJ, Kim J, Houk KN, Movassaghi M, Sherman DH J Am Chem Soc. 2020 Oct 14;142(41):17413-17424. doi: 10.1021/jacs.0c06312. Epub, 2020 Sep 30. PMID:32786740<ref>PMID:32786740</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 6xai" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Streptomyces sp. ~~nrrl f~~-5053]]	+	[[Category: Streptomyces sp. NRRL F-5053]]
-	[[Category: Doyon~~, T J~~]]	+	[[Category: Doyon TJ]]
-	[[Category: Houk~~, K N~~]]	+	[[Category: Houk KN]]
-	[[Category: Khatri, Y]]	+	[[Category: Khatri Y]]
-	[[Category: Kim, J]]	+	[[Category: Kim J]]
-	[[Category: Lindovska, P]]	+	[[Category: Lindovska P]]
-	[[Category: Movassaghi, M]]	+	[[Category: Movassaghi M]]
-	[[Category: Newmister~~, S A~~]]	+	[[Category: Newmister SA]]
-	[[Category: Sanders~~, J N~~]]	+	[[Category: Sanders JN]]
-	[[Category: Shende~~, V V~~]]	+	[[Category: Shende VV]]
-	[[Category: Sherman~~, D H~~]]	+	[[Category: Sherman DH]]
-	[[Category: Yu, F]]	+	[[Category: Yu F]]
-	~~[[Category: Dimerase]]~~	+
-	~~[[Category: Monooxygenase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: P450~~]]	+

OCA at 15:32, 22 December 2021

OCA — Wed, 22 Dec 2021 15:32:19 GMT

←Older revision		Revision as of 15:32, 22 December 2021
Line 1:		Line 1:

	==Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)==		==Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)==
-	<StructureSection load='6xai' size='340' side='right'caption='[[6xai]]' scene=''>	+	<StructureSection load='6xai' size='340' side='right'caption='[[6xai]], [[Resolution\|resolution]] 1.49Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xai]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._nrrl_f-5053 Streptomyces sp. nrrl f-5053]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br>
-	</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=QRP:(3S,8AS)-3-(1H-INDOL-3-YLMETHYL)HEXAHYDROPYRROLO[1,2-A]PYRAZINE-1,4-DIONE'>QRP</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The dimeric diketopiperazine (DKPs) alkaloids are a diverse family of natural products (NPs) whose unique structural architectures and biological activities have inspired the development of new synthetic methodologies to access these molecules. However, catalyst-controlled methods that enable the selective formation of constitutional and stereoisomeric dimers from a single monomer are lacking. To resolve this long-standing synthetic challenge, we sought to characterize the biosynthetic enzymes that assemble these NPs for application in biocatalytic syntheses. Genome mining enabled identification of the cytochrome P450, NzeB (Streptomyces sp. NRRL F-5053), which catalyzes both intermolecular carbon-carbon (C-C) and carbon-nitrogen (C-N) bond formation. To identify the molecular basis for the flexible site-selectivity, stereoselectivity, and chemoselectivity of NzeB, we obtained high-resolution crystal structures (1.5 A) of the protein in complex with native and non-native substrates. This, to our knowledge, represents the first crystal structure of an oxidase catalyzing direct, intermolecular C-H amination. Site-directed mutagenesis was utilized to assess the role individual active-site residues play in guiding selective DKP dimerization. Finally, computational approaches were employed to evaluate plausible mechanisms regarding NzeB function and its ability to catalyze both C-C and C-N bond formation. These results provide a structural and computational rationale for the catalytic versatility of NzeB, as well as new insights into variables that control selectivity of CYP450 diketopiperazine dimerases.
		+
		+	Structure and Function of NzeB, a Versatile C-C and C-N Bond-Forming Diketopiperazine Dimerase.,Shende VV, Khatri Y, Newmister SA, Sanders JN, Lindovska P, Yu F, Doyon TJ, Kim J, Houk KN, Movassaghi M, Sherman DH J Am Chem Soc. 2020 Oct 14;142(41):17413-17424. doi: 10.1021/jacs.0c06312. Epub, 2020 Sep 30. PMID:32786740<ref>PMID:32786740</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xai" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Doyon TJ]]	+	[[Category: Streptomyces sp. nrrl f-5053]]
-	[[Category: Houk KN]]	+	[[Category: Doyon, T J]]
-	[[Category: Khatri Y]]	+	[[Category: Houk, K N]]
-	[[Category: Kim J]]	+	[[Category: Khatri, Y]]
-	[[Category: Lindovska P]]	+	[[Category: Kim, J]]
-	[[Category: Movassaghi M]]	+	[[Category: Lindovska, P]]
-	[[Category: Newmister SA]]	+	[[Category: Movassaghi, M]]
-	[[Category: Sanders JN]]	+	[[Category: Newmister, S A]]
-	[[Category: Shende VV]]	+	[[Category: Sanders, J N]]
-	[[Category: Sherman DH]]	+	[[Category: Shende, V V]]
-	[[Category: Yu F]]	+	[[Category: Sherman, D H]]
		+	[[Category: Yu, F]]
		+	[[Category: Dimerase]]
		+	[[Category: Monooxygenase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: P450]]

OCA at 12:09, 9 June 2021

OCA — Wed, 09 Jun 2021 12:09:26 GMT

←Older revision		Revision as of 12:09, 9 June 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6xai is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)==
-		+	<StructureSection load='6xai' size='340' side='right'caption='[[6xai]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XAI FirstGlance]. <br>
-	~~Description~~:	+	</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=6xai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xai OCA], [https://pdbe.org/6xai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xai RCSB], [https://www.ebi.ac.uk/pdbsum/6xai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xai ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Doyon TJ]]
		+	[[Category: Houk KN]]
		+	[[Category: Khatri Y]]
		+	[[Category: Kim J]]
		+	[[Category: Lindovska P]]
		+	[[Category: Movassaghi M]]
		+	[[Category: Newmister SA]]
		+	[[Category: Sanders JN]]
		+	[[Category: Shende VV]]
		+	[[Category: Sherman DH]]
		+	[[Category: Yu F]]

OCA at 10:44, 8 July 2020

OCA — Wed, 08 Jul 2020 10:44:33 GMT

←Older revision		Revision as of 10:44, 8 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xai is ON HOLD	+	The entry 6xai is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 08:38, 17 June 2020

OCA — Wed, 17 Jun 2020 08:38:35 GMT

←Older revision		Revision as of 08:38, 17 June 2020
Line 3:		Line 3:
	The entry 6xai is ON HOLD		The entry 6xai is ON HOLD

-	Authors: ~~Shende, V.V., Khatri, Y., Newmister, S.A., Sanders, J.N., Lindovska, P., Yu, F., Doyon, T.J., Kim, J., Movassaghi, M., Houk, K.N., Sherman, D.H.~~	+	Authors:

-	Description: ~~Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Newmister, S.A]]
-	[[Category: Khatri, Y]]
-	[[Category: Sherman, D.H]]
-	[[Category: Yu, F]]
-	[[Category: Movassaghi, M]]
-	[[Category: Sanders, J.N]]
-	[[Category: Lindovska, P]]
-	[[Category: Houk, K.N]]
-	[[Category: Shende, V.V]]
-	[[Category: Kim, J]]
-	[[Category: Doyon, T.J]]

OCA: Protected "6xai" [edit=sysop:move=sysop]

OCA — Wed, 10 Jun 2020 05:03:24 GMT

Protected "6xai" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:03, 10 June 2020

OCA: New page: '''Unreleased structure''' The entry 6xai is ON HOLD Authors: Shende, V.V., Khatri, Y., Newmister, S.A., Sanders, J.N., Lindovska, P., Yu, F., Doyon, T.J., Kim, J., Movassaghi, M., Houk...

OCA — Wed, 10 Jun 2020 05:03:23 GMT

New page: '''Unreleased structure''' The entry 6xai is ON HOLD Authors: Shende, V.V., Khatri, Y., Newmister, S.A., Sanders, J.N., Lindovska, P., Yu, F., Doyon, T.J., Kim, J., Movassaghi, M., Houk...

New page

'''Unreleased structure'''

The entry 6xai is ON HOLD

Authors: Shende, V.V., Khatri, Y., Newmister, S.A., Sanders, J.N., Lindovska, P., Yu, F., Doyon, T.J., Kim, J., Movassaghi, M., Houk, K.N., Sherman, D.H.

Description: Crystal structure of NzeB in complex with cyclo-(L-Trp-L-Pro)
[[Category: Unreleased Structures]]
[[Category: Newmister, S.A]]
[[Category: Khatri, Y]]
[[Category: Sherman, D.H]]
[[Category: Yu, F]]
[[Category: Movassaghi, M]]
[[Category: Sanders, J.N]]
[[Category: Lindovska, P]]
[[Category: Houk, K.N]]
[[Category: Shende, V.V]]
[[Category: Kim, J]]
[[Category: Doyon, T.J]]