5jgb - Revision history

OCA at 11:03, 6 September 2023

2023-09-06T11:03:05Z

← Older revision		Revision as of 11:03, 6 September 2023
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	<StructureSection load='5jgb' size='340' side='right'caption='[[5jgb]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='5jgb' size='340' side='right'caption='[[5jgb]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5jgb]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JGB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5JGB FirstGlance]. <br>		<table><tr><td colspan='2'>[[5jgb]] is a 1 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=5JGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JGB FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=6JV:N-(2-METHOXY-4-{[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]CARBAMOYL}PHENYL)~~-~~4-OXO-3~~,~~4-DIHYDROTHIENO~~[~~3,2-D]PYRIMIDINE-7-CARBOXAMIDE'>6JV</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='related'><td class="sblockLbl"><b>~~[~~[Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[5jga\|5jga]], [[5jgd\|5jgd~~]]</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6JV:N-(2-METHOXY-4-{[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]CARBAMOYL}PHENYL)-4-OXO-3,4-DIHYDROTHIENO[3,2-D]PYRIMIDINE-7-CARBOXAMIDE'>6JV</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>TAB1, MAP3K7IP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=5jgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jgb OCA], [https://pdbe.org/5jgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jgb RCSB], [https://www.ebi.ac.uk/pdbsum/5jgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jgb ProSAT]</span></td></tr>
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/Mitogen~~-~~activated_protein_kinase_kinase_kinase Mitogen~~-~~activated protein kinase kinase kinase~~], ~~with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=2.~~7~~.11.25 2.7.11.25]~~ </~~span~~></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5jgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jgb OCA], [~~http~~://pdbe.org/5jgb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5jgb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5jgb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5jgb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>		[https://www.uniprot.org/uniprot/TAB1_HUMAN TAB1_HUMAN] May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.<ref>PMID:16879102</ref> [https://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>
	<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: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Mitogen-activated protein kinase kinase kinase]]~~		[[Category: Fukami TA]]
	[[Category: Fukami~~, T A~~]]		[[Category: Irie M]]
	[[Category: Irie, M]]		[[Category: Matsuura T]]
	[[Category: Matsuura, T]]		[[Category: Morishima K]]
	[[Category: Morishima, K]]		[[Category: Nakamura M]]
	[[Category: Nakamura, M]]
	~~[[Category: Tak1-tab1 kinase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 07:48, 10 June 2020

2020-06-10T07:48:01Z

← Older revision		Revision as of 07:48, 10 June 2020
Line 1:		Line 1:

	==Crystal structure of human TAK1/TAB1 fusion protein in complex with ligand 10==		==Crystal structure of human TAK1/TAB1 fusion protein in complex with ligand 10==
	<StructureSection load='5jgb' size='340' side='right' caption='[[5jgb]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='5jgb' size='340' side='right'caption='[[5jgb]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5jgb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JGB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5JGB FirstGlance]. <br>		<table><tr><td colspan='2'>[[5jgb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JGB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JGB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JV:N-(2-METHOXY-4-{[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]CARBAMOYL}PHENYL)-4-OXO-3,4-DIHYDROTHIENO[3,2-D]PYRIMIDINE-7-CARBOXAMIDE'>6JV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6JV:N-(2-METHOXY-4-{[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]CARBAMOYL}PHENYL)-4-OXO-3,4-DIHYDROTHIENO[3,2-D]PYRIMIDINE-7-CARBOXAMIDE'>6JV</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jga\|5jga]], [[5jgd\|5jgd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5jga\|5jga]], [[5jgd\|5jgd]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TAB1, MAP3K7IP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5jgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jgb OCA], [http://pdbe.org/5jgb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jgb RCSB], [http://www.ebi.ac.uk/pdbsum/5jgb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jgb ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jgb OCA], [http://pdbe.org/5jgb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jgb RCSB], [http://www.ebi.ac.uk/pdbsum/5jgb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jgb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	</div>		</div>
	<div class="pdbe-citations 5jgb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5jgb" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Mitogen-activated protein kinase kinase kinase\|Mitogen-activated protein kinase kinase kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Fukami, T A]]		[[Category: Fukami, T A]]

OCA at 04:38, 9 September 2016

2016-09-09T04:38:48Z

← Older revision		Revision as of 04:38, 9 September 2016
Line 11:		Line 11:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>		[[http://www.uniprot.org/uniprot/M3K7_HUMAN M3K7_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.<ref>PMID:8663074</ref> <ref>PMID:9079627</ref> <ref>PMID:10094049</ref> <ref>PMID:11460167</ref> <ref>PMID:12589052</ref> <ref>PMID:16845370</ref> <ref>PMID:16893890</ref> <ref>PMID:21512573</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			A novel thienopyrimidinone analog was discovered as a potent and highly selective TAK1 inhibitor using the SBDD approach. TAK1 plays a key role in inflammatory and immune signaling, so TAK1 is considered to be an attractive molecular target for the treatment of human diseases (inflammatory disease, cancer, etc.). After the hit compound had been obtained, our modifications successfully increased TAK1 inhibitory activity and solubility, but metabolic stability was still unsatisfactory. To improve metabolic stability, we conducted metabolic identification. Although the obtained metabolite was fortunately a potent TAK1 inhibitor, its kinase selectivity was low. Subsequently, to achieve high kinase selectivity, we used SBDD to follow two strategies: one targeting unique amino acid residues in TAK1, especially the combination of Ser111 and Asn114; the other decreasing the interaction with Tyr106 at the hinge position in TAK1. As expected, our designed compound showed an excellent kinase selectivity profile in both an in-house and a commercially available panel assay of over 420 kinases and also retained its potent TAK1 inhibitory activity (TAK1 IC50=11nM).

			Discovery of a potent and highly selective transforming growth factor beta receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD).,Muraoka T, Ide M, Morikami K, Irie M, Nakamura M, Miura T, Kamikawa T, Nishihara M, Kashiwagi H Bioorg Med Chem. 2016 Sep 15;24(18):4206-17. doi: 10.1016/j.bmc.2016.07.006. Epub, 2016 Jul 6. PMID:27448772<ref>PMID:27448772</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5jgb" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:45, 27 July 2016

2016-07-27T15:45:25Z

@@ Line 1: / Line 1: @@
-The entry 5jgb is ON HOLD  until Paper Publication
+==Crystal structure of human TAK1/TAB1 fusion protein in complex with ligand 10==
+<StructureSection load='5jgb' size='340' side='right' caption='[[5jgb]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5jgb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JGB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JGB FirstGlance]. <br>
-Description:
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JV:N-(2-METHOXY-4-{[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]CARBAMOYL}PHENYL)-4-OXO-3,4-DIHYDROTHIENO[3,2-D]PYRIMIDINE-7-CARBOXAMIDE'>6JV</scene></td></tr>
-[[Category: Unreleased Structures]]
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jga|5jga]], [[5jgd|5jgd]]</td></tr>

OCA at 15:23, 15 May 2016

2016-05-15T15:23:15Z

← Older revision		Revision as of 15:23, 15 May 2016
Line 3:		Line 3:
	The entry 5jgb is ON HOLD until Paper Publication		The entry 5jgb is ON HOLD until Paper Publication

	Authors: ~~Irie, M., Nakamura, M., Fukami, T.A., Matsuura, T., Morishima, K.~~		Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: Morishima, K]]~~
	~~[[Category: Matsuura, T]]~~
	~~[[Category: Nakamura, M]]~~
	~~[[Category: Irie, M]]~~
	~~[[Category: Fukami, T.A]]~~

OCA: Protected "5jgb" [edit=sysop:move=sysop]

2016-05-11T02:00:53Z

Protected "5jgb" [edit=sysop:move=sysop]

← Older revision	Revision as of 02:00, 11 May 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5jgb is ON HOLD until Paper Publication Authors: Irie, M., Nakamura, M., Fukami, T.A., Matsuura, T., Morishima, K. Description: [[Category: Unrele...

2016-05-11T02:00:52Z

New page: '''Unreleased structure''' The entry 5jgb is ON HOLD until Paper Publication Authors: Irie, M., Nakamura, M., Fukami, T.A., Matsuura, T., Morishima, K. Description: [[Category: Unrele...

New page

'''Unreleased structure'''

The entry 5jgb is ON HOLD until Paper Publication

Authors: Irie, M., Nakamura, M., Fukami, T.A., Matsuura, T., Morishima, K.

Description:
[[Category: Unreleased Structures]]
[[Category: Morishima, K]]
[[Category: Matsuura, T]]
[[Category: Nakamura, M]]
[[Category: Irie, M]]
[[Category: Fukami, T.A]]