OCA at 08:16, 16 August 2023

OCA — Wed, 16 Aug 2023 08:16:14 GMT

←Older revision		Revision as of 08:16, 16 August 2023
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-	'''Unreleased structure'''

-	The ~~entry~~ 7yix is ~~ON HOLD~~	+	==The Cryo-EM Structure of Human Tissue Nonspecific Alkaline Phosphatase and Single-Chain Fragment Variable (ScFv) Complex.==
		+	<StructureSection load='7yix' size='340' side='right'caption='[[7yix]], [[Resolution\|resolution]] 2.96Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7yix]] is a 4 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=7YIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YIX FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.96Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7yix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yix OCA], [https://pdbe.org/7yix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yix RCSB], [https://www.ebi.ac.uk/pdbsum/7yix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yix ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/PPBT_HUMAN PPBT_HUMAN] Prenatal benign hypophosphatasia;Infantile hypophosphatasia;Odontohypophosphatasia;Perinatal lethal hypophosphatasia;Childhood-onset hypophosphatasia;Adult hypophosphatasia. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PPBT_HUMAN PPBT_HUMAN] Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:12162492, PubMed:2220817). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:23688511, PubMed:25982064). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:2220817, PubMed:20049532). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (PubMed:28448526). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity).[UniProtKB:P09242]<ref>PMID:12162492</ref> <ref>PMID:20049532</ref> <ref>PMID:2220817</ref> <ref>PMID:23688511</ref> <ref>PMID:25982064</ref> <ref>PMID:28448526</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hypophosphatasia (HPP) is a metabolic bone disease that manifests as developmental abnormalities in bone and dental tissues. HPP patients exhibit hypo-mineralization and osteopenia due to the deficiency or malfunction of tissue non-specific alkaline phosphatase (TNAP), which catalyzes the hydrolysis of phosphate-containing molecules outside the cells, promoting the deposition of hydroxyapatite in the extracellular matrix. Despite the identification of hundreds of pathogenic TNAP mutations, the detailed molecular pathology of HPP remains unclear. Here, to address this issue, we determine the crystal structures of human TNAP at near-atomic resolution and map the major pathogenic mutations onto the structure. Our study reveals an unexpected octameric architecture for TNAP, which is generated by the tetramerization of dimeric TNAPs, potentially stabilizing the TNAPs in the extracellular environments. Moreover, we use cryo-electron microscopy to demonstrate that the TNAP agonist antibody (JTALP001) forms a stable complex with TNAP by binding to the octameric interface. The administration of JTALP001 enhances osteoblast mineralization and promoted recombinant TNAP-rescued mineralization in TNAP knockout osteoblasts. Our findings elucidate the structural pathology of HPP and highlight the therapeutic potential of the TNAP agonist antibody for osteoblast-associated bone disorders.

-	~~Authors:~~ Yu, ~~Y.T.~~, Yao, D~~.Q.~~, Zhang, Q., ~~Rao~~, B., Xia, Y., Lu, Y., ~~Qin~~, A., Ma, P~~.X.~~, Cao, Y.	+	The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase.,Yu Y, Rong K, Yao D, Zhang Q, Cao X, Rao B, Xia Y, Lu Y, Shen Y, Yao Y, Xu H, Ma P, Cao Y, Qin A Nat Commun. 2023 Jul 8;14(1):4048. doi: 10.1038/s41467-023-39833-3. PMID:37422472<ref>PMID:37422472</ref>

-	~~Description: The Cryo-EM Structure~~ of ~~Human Tissue Nonspecific Alkaline Phosphatase and Single-Chain Fragment Variable (ScFv) Complex~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Cao, Y]]	+	<div class="pdbe-citations 7yix" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Qin, A~~]]	+	== References ==
-	[[Category: ~~Rao, B~~]]	+	<references/>
-	[[Category: ~~Yu, Y.T~~]]	+	__TOC__
-	[[Category: ~~Ma, P.X~~]]	+	</StructureSection>
-	[[Category: ~~Lu,~~ Y]]	+	[[Category: Homo sapiens]]
-	[[Category: Yao~~, D.Q~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Xia, Y~~]]	+	[[Category: Cao Y]]
-	[[Category: Zhang, Q]]	+	[[Category: Lu Y]]
		+	[[Category: Ma PX]]
		+	[[Category: Qin A]]
		+	[[Category: Rao B]]
		+	[[Category: Xia Y]]
		+	[[Category: Yao DQ]]
		+	[[Category: Yu YT]]
		+	[[Category: Zhang Q]]

OCA at 03:46, 9 August 2023

OCA — Wed, 09 Aug 2023 03:46:41 GMT

←Older revision		Revision as of 03:46, 9 August 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yix is ON HOLD ~~until Paper Publication~~	+	The entry 7yix is ON HOLD

	Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y.		Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y.

OCA at 05:18, 31 August 2022

OCA — Wed, 31 Aug 2022 05:18:12 GMT

←Older revision		Revision as of 05:18, 31 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yix is ON HOLD	+	The entry 7yix is ON HOLD until Paper Publication

	Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y.		Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y.

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

OCA — Wed, 27 Jul 2022 16:26:52 GMT

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

←Older revision

Revision as of 16:26, 27 July 2022

OCA: New page: '''Unreleased structure''' The entry 7yix is ON HOLD Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y. Description: The Cryo-EM Structure of...

OCA — Wed, 27 Jul 2022 16:26:51 GMT

New page: '''Unreleased structure''' The entry 7yix is ON HOLD Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y. Description: The Cryo-EM Structure of...

New page

'''Unreleased structure'''

The entry 7yix is ON HOLD

Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y.

Description: The Cryo-EM Structure of Human Tissue Nonspecific Alkaline Phosphatase and Single-Chain Fragment Variable (ScFv) Complex.
[[Category: Unreleased Structures]]
[[Category: Cao, Y]]
[[Category: Qin, A]]
[[Category: Rao, B]]
[[Category: Yu, Y.T]]
[[Category: Ma, P.X]]
[[Category: Lu, Y]]
[[Category: Yao, D.Q]]
[[Category: Xia, Y]]
[[Category: Zhang, Q]]

7yix - Revision history

OCA at 08:16, 16 August 2023

OCA at 03:46, 9 August 2023

OCA at 05:18, 31 August 2022

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

OCA: New page: '''Unreleased structure''' The entry 7yix is ON HOLD Authors: Yu, Y.T., Yao, D.Q., Zhang, Q., Rao, B., Xia, Y., Lu, Y., Qin, A., Ma, P.X., Cao, Y. Description: The Cryo-EM Structure of...