7cd0 - Revision history

OCA at 10:55, 23 October 2024

2024-10-23T10:55:05Z

← Older revision		Revision as of 10:55, 23 October 2024
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	<StructureSection load='7cd0' size='340' side='right'caption='[[7cd0]], [[Resolution\|resolution]] 2.31Å' scene=''>		<StructureSection load='7cd0' size='340' side='right'caption='[[7cd0]], [[Resolution\|resolution]] 2.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7cd0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD0 FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD0 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]] 2.31Å</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]] 2.31Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7J8:3-[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-3-(3-hydroxy-3-oxopropyl)-5-methyl-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-1~{H}-pyrrol-3-yl]propanoic+acid'>7J8</scene>, <scene name='pdbligand=FWL:3-[5-(aminomethyl)-4-(carboxymethyl)-2-iodo-1H-pyrrol-3-yl]propanoic+acid'>FWL</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7J8:3-[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-3-(3-hydroxy-3-oxopropyl)-5-methyl-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-1~{H}-pyrrol-3-yl]propanoic+acid'>7J8</scene>, <scene name='pdbligand=FWL:3-[5-(aminomethyl)-4-(carboxymethyl)-2-iodo-1H-pyrrol-3-yl]propanoic+acid'>FWL</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=7cd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd0 OCA], [https://pdbe.org/7cd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd0 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=7cd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd0 OCA], [https://pdbe.org/7cd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd0 ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[https://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN] Defects in HMBS are the cause of acute intermittent porphyria (AIP) [MIM:[https://omim.org/entry/176000 176000]. AIP is a form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by acute attacks of neurological dysfunctions with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.<ref>PMID:2243128</ref> <ref>PMID:1714233</ref> <ref>PMID:1496994</ref> <ref>PMID:1427766</ref> <ref>PMID:1301948</ref> <ref>PMID:8262523</ref> <ref>PMID:8401516</ref> <ref>PMID:8268934</ref> <ref>PMID:8270254</ref> <ref>PMID:8270256</ref> <ref>PMID:8081367</ref> <ref>PMID:7962538</ref> <ref>PMID:7757070</ref> <ref>PMID:8825929</ref> <ref>PMID:9199558</ref> <ref>PMID:9225970</ref> <ref>PMID:9654202</ref> <ref>PMID:9463797</ref> <ref>PMID:10494093</ref> <ref>PMID:10453740</ref> <ref>PMID:10502788</ref> <ref>PMID:10657149</ref> <ref>PMID:10602775</ref> <ref>PMID:11399210</ref> <ref>PMID:11030413</ref> <ref>PMID:10782018</ref> <ref>PMID:11013452</ref> [:]<ref>PMID:12406973</ref> <ref>PMID:12372055</ref> <ref>PMID:11857754</ref> <ref>PMID:14669009</ref> <ref>PMID:14970743</ref> <ref>PMID:15669678</ref>
	~~== Function ==~~
	~~[https://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN] Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.~~
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Homo sapiens]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Hirabayashi K]]		[[Category: Hirabayashi K]]

OCA at 16:04, 29 November 2023

2023-11-29T16:04:44Z

← Older revision		Revision as of 16:04, 29 November 2023
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	==Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase==		==Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase==
	<StructureSection load='7cd0' size='340' side='right'caption='[[7cd0]]' scene=''>		<StructureSection load='7cd0' size='340' side='right'caption='[[7cd0]], [[Resolution\|resolution]] 2.31Å' 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=7CD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7cd0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD0 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=7cd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd0 OCA], [https://pdbe.org/7cd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd0 ProSAT]</span></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]] 2.31Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7J8:3-[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-3-(3-hydroxy-3-oxopropyl)-5-methyl-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-1~{H}-pyrrol-3-yl]propanoic+acid'>7J8</scene>, <scene name='pdbligand=FWL:3-[5-(aminomethyl)-4-(carboxymethyl)-2-iodo-1H-pyrrol-3-yl]propanoic+acid'>FWL</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=7cd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd0 OCA], [https://pdbe.org/7cd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd0 ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN] Defects in HMBS are the cause of acute intermittent porphyria (AIP) [MIM:[https://omim.org/entry/176000 176000]. AIP is a form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by acute attacks of neurological dysfunctions with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.<ref>PMID:2243128</ref> <ref>PMID:1714233</ref> <ref>PMID:1496994</ref> <ref>PMID:1427766</ref> <ref>PMID:1301948</ref> <ref>PMID:8262523</ref> <ref>PMID:8401516</ref> <ref>PMID:8268934</ref> <ref>PMID:8270254</ref> <ref>PMID:8270256</ref> <ref>PMID:8081367</ref> <ref>PMID:7962538</ref> <ref>PMID:7757070</ref> <ref>PMID:8825929</ref> <ref>PMID:9199558</ref> <ref>PMID:9225970</ref> <ref>PMID:9654202</ref> <ref>PMID:9463797</ref> <ref>PMID:10494093</ref> <ref>PMID:10453740</ref> <ref>PMID:10502788</ref> <ref>PMID:10657149</ref> <ref>PMID:10602775</ref> <ref>PMID:11399210</ref> <ref>PMID:11030413</ref> <ref>PMID:10782018</ref> <ref>PMID:11013452</ref> [:]<ref>PMID:12406973</ref> <ref>PMID:12372055</ref> <ref>PMID:11857754</ref> <ref>PMID:14669009</ref> <ref>PMID:14970743</ref> <ref>PMID:15669678</ref>
			== Function ==
			[https://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN] Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Hydroxymethylbilane synthase (HMBS), which is involved in the heme biosynthesis pathway, has a dipyrromethane cofactor and combines four porphobilinogen (PBG) molecules to form a linear tetrapyrrole, hydroxymethylbilane. Enzyme kinetic study of human HMBS using a PBG-derivative, 2-iodoporphobilinogen (2-I-PBG), exhibited noncompetitive inhibition with the inhibition constant being 5.4 +/- 0.3 microM. To elucidate the reaction mechanism of HMBS in detail, crystal structure analysis of 2-I-PBG-bound holo-HMBS and its reaction intermediate possessing two PBG molecules (ES2), and inhibitor-free ES2 was performed at 2.40, 2.31, and 1.79 A resolution, respectively. Their overall structures are similar to that of inhibitor-free holo-HMBS, and the differences are limited near the active site. In both 2-I-PBG-bound structures, 2-I-PBG is located near the terminus of the cofactor or the tetrapyrrole chain. The propionate group of 2-I-PBG interacts with the side chain of Arg173, and its acetate group is associated with the side chains of Arg26 and Ser28. Furthermore, the aminomethyl group and pyrrole nitrogen of 2-I-PBG form hydrogen bonds with the side chains of Gln34 and Asp99, respectively. These amino acid residues form a single substrate-binding site, where each of the four PBG molecules covalently binds to the cofactor (or oligopyrrole chain) consecutively, ultimately forming a hexapyrrole chain. Molecular dynamics simulation of the ES2 intermediate suggested that the thermal fluctuation of the lid and cofactor-binding loops causes substrate recruitment and oligopyrrole chain shift needed for consecutive condensation. Finally, the hexapyrrole chain is hydrolyzed self-catalytically to produce hydroxymethylbilane.

			Crystal structures of hydroxymethylbilane synthase complexed with a substrate analog: a single substrate-binding site for four consecutive condensation steps.,Sato H, Sugishima M, Tsukaguchi M, Masuko T, Iijima M, Takano M, Omata Y, Hirabayashi K, Wada K, Hisaeda Y, Yamamoto K Biochem J. 2021 Mar 12;478(5):1023-1042. doi: 10.1042/BCJ20200996. PMID:33600566<ref>PMID:33600566</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7cd0" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Porphobilinogen Deaminase\|Porphobilinogen Deaminase]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Hirabayashi K]]		[[Category: Hirabayashi K]]

OCA at 06:46, 17 March 2021

2021-03-17T06:46:11Z

← Older revision		Revision as of 06:46, 17 March 2021
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7cd0 is ~~ON HOLD until Paper Publication~~		==Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase==
			<StructureSection load='7cd0' size='340' side='right'caption='[[7cd0]]' scene=''>
	~~Authors~~: ~~Sato~~, H., ~~Sugishima~~, M., ~~Wada, K~~., ~~Hirabayashi, K~~.~~, Tsukaguchi, M~~.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD0 FirstGlance]. <br>
	~~Description: Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase~~		</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=7cd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd0 OCA], [https://pdbe.org/7cd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd0 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd0 ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: ~~Tsukaguchi, M~~]]		__TOC__
	[[Category: ~~Wada, K~~]]		</StructureSection>
	[[Category: Sugishima, M]]		[[Category: Large Structures]]
	[[Category: ~~Hirabayashi, K~~]]		[[Category: Hirabayashi K]]
	[[Category: ~~Sato, H~~]]		[[Category: Sato H]]
			[[Category: Sugishima M]]
			[[Category: Tsukaguchi M]]
			[[Category: Wada K]]

OCA at 11:25, 8 July 2020

2020-07-08T11:25:01Z

← Older revision		Revision as of 11:25, 8 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7cd0 is ON HOLD		The entry 7cd0 is ON HOLD until Paper Publication

	Authors: Sato, H., Sugishima, M., Wada, K., Hirabayashi, K., Tsukaguchi, M.		Authors: Sato, H., Sugishima, M., Wada, K., Hirabayashi, K., Tsukaguchi, M.
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	Description: Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase		Description: Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Tsukaguchi, M]]
			[[Category: Wada, K]]
	[[Category: Sugishima, M]]		[[Category: Sugishima, M]]
	[[Category: Hirabayashi, K]]		[[Category: Hirabayashi, K]]
	[[Category: Sato, H]]		[[Category: Sato, H]]
	~~[[Category: Tsukaguchi, M]]~~
	~~[[Category: Wada, K]]~~

OCA: Protected "7cd0" [edit=sysop:move=sysop]

2020-06-24T18:55:42Z

Protected "7cd0" [edit=sysop:move=sysop]

← Older revision	Revision as of 18:55, 24 June 2020
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7cd0 is ON HOLD Authors: Sato, H., Sugishima, M., Wada, K., Hirabayashi, K., Tsukaguchi, M. Description: Crystal structure of the 2-iodoporphobilin...

2020-06-24T18:55:39Z

New page: '''Unreleased structure''' The entry 7cd0 is ON HOLD Authors: Sato, H., Sugishima, M., Wada, K., Hirabayashi, K., Tsukaguchi, M. Description: Crystal structure of the 2-iodoporphobilin...

New page

'''Unreleased structure'''

The entry 7cd0 is ON HOLD

Authors: Sato, H., Sugishima, M., Wada, K., Hirabayashi, K., Tsukaguchi, M.

Description: Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase
[[Category: Unreleased Structures]]
[[Category: Sugishima, M]]
[[Category: Hirabayashi, K]]
[[Category: Sato, H]]
[[Category: Tsukaguchi, M]]
[[Category: Wada, K]]