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| - | {{STRUCTURE_1zwd| PDB=1zwd | SCENE= }}
| + | ==STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 3-37, NMR, 10 STRUCTURES== |
| - | ===STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 3-37, NMR, 10 STRUCTURES===
| + | <StructureSection load='1zwd' size='340' side='right' caption='[[1zwd]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
| - | {{ABSTRACT_PUBMED_9468478}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1zwd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZWD FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POTENTIAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zwd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1zwd RCSB], [http://www.ebi.ac.uk/pdbsum/1zwd PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/PTHY_HUMAN PTHY_HUMAN]] Defects in PTH are a cause of familial isolated hypoparathyroidism (FIH) [MIM:[http://omim.org/entry/146200 146200]]; also called autosomal dominant hypoparathyroidism or autosomal dominant hypocalcemia. FIH is characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. FIH exist both as autosomal dominant and recessive forms of hypoparathyroidism.<ref>PMID:2212001</ref> <ref>PMID:10523031</ref> <ref>PMID:18056632</ref> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/PTHY_HUMAN PTHY_HUMAN]] PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells.<ref>PMID:21076856</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zw/1zwd_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Human parathyroid hormone (hPTH) is involved in the regulation of the calcium level in blood. This hormone function is located in the NH2-terminal 34 amino acids of the 84-amino acid peptide hormone and is transduced via the adenylate cyclase and the phosphatidylinositol signaling pathways. It is well known that truncation of the two NH2-terminal amino acids of the hormone leads to complete loss of in vivo normocalcemic function. To correlate loss of calcium level regulatory activity after stepwise NH2-terminal truncation and solution structure, we studied the conformations of fragments hPTH-(2-37), hPTH-(3-37), and hPTH-(4-37) in comparison to hPTH-(1-37) in aqueous buffer solution under near physiological conditions by circular dichroism spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, and restrained molecular dynamics calculations. All peptides show helical structures and hydrophobic interactions between Leu-15 and Trp-23 that lead to a defined loop region from His-14 to Ser-17. A COOH-terminal helix from Met-18 to at least Leu-28 was found for all peptides. The helical structure in the NH2-terminal part of the peptides was lost in parallel with the NH2-terminal truncation and can be correlated with the loss of calcium regulatory activity. |
| | | | |
| - | ==Disease==
| + | Structure-activity relation of NH2-terminal human parathyroid hormone fragments.,Marx UC, Adermann K, Bayer P, Meyer M, Forssmann WG, Rosch P J Biol Chem. 1998 Feb 20;273(8):4308-16. PMID:9468478<ref>PMID:9468478</ref> |
| - | [[http://www.uniprot.org/uniprot/PTHY_HUMAN PTHY_HUMAN]] Defects in PTH are a cause of familial isolated hypoparathyroidism (FIH) [MIM:[http://omim.org/entry/146200 146200]]; also called autosomal dominant hypoparathyroidism or autosomal dominant hypocalcemia. FIH is characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. FIH exist both as autosomal dominant and recessive forms of hypoparathyroidism.<ref>PMID:2212001</ref><ref>PMID:10523031</ref><ref>PMID:18056632</ref>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/PTHY_HUMAN PTHY_HUMAN]] PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells.<ref>PMID:21076856</ref>
| + | </div> |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | [[1zwd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZWD OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | <references group="xtra"/><references/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Marx, U C.]] | | [[Category: Marx, U C.]] |
| Structural highlights
1zwd is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | POTENTIAL (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[PTHY_HUMAN] Defects in PTH are a cause of familial isolated hypoparathyroidism (FIH) [MIM:146200]; also called autosomal dominant hypoparathyroidism or autosomal dominant hypocalcemia. FIH is characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. FIH exist both as autosomal dominant and recessive forms of hypoparathyroidism.[1] [2] [3]
Function
[PTHY_HUMAN] PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human parathyroid hormone (hPTH) is involved in the regulation of the calcium level in blood. This hormone function is located in the NH2-terminal 34 amino acids of the 84-amino acid peptide hormone and is transduced via the adenylate cyclase and the phosphatidylinositol signaling pathways. It is well known that truncation of the two NH2-terminal amino acids of the hormone leads to complete loss of in vivo normocalcemic function. To correlate loss of calcium level regulatory activity after stepwise NH2-terminal truncation and solution structure, we studied the conformations of fragments hPTH-(2-37), hPTH-(3-37), and hPTH-(4-37) in comparison to hPTH-(1-37) in aqueous buffer solution under near physiological conditions by circular dichroism spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, and restrained molecular dynamics calculations. All peptides show helical structures and hydrophobic interactions between Leu-15 and Trp-23 that lead to a defined loop region from His-14 to Ser-17. A COOH-terminal helix from Met-18 to at least Leu-28 was found for all peptides. The helical structure in the NH2-terminal part of the peptides was lost in parallel with the NH2-terminal truncation and can be correlated with the loss of calcium regulatory activity.
Structure-activity relation of NH2-terminal human parathyroid hormone fragments.,Marx UC, Adermann K, Bayer P, Meyer M, Forssmann WG, Rosch P J Biol Chem. 1998 Feb 20;273(8):4308-16. PMID:9468478[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM. Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J Clin Invest. 1990 Oct;86(4):1084-7. PMID:2212001 doi:http://dx.doi.org/10.1172/JCI114811
- ↑ Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S. A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism. J Clin Endocrinol Metab. 1999 Oct;84(10):3792-6. PMID:10523031
- ↑ Datta R, Waheed A, Shah GN, Sly WS. Signal sequence mutation in autosomal dominant form of hypoparathyroidism induces apoptosis that is corrected by a chemical chaperone. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19989-94. Epub 2007 Dec 3. PMID:18056632 doi:10.1073/pnas.0708725104
- ↑ Zoidis E, Ghirlanda-Keller C, Schmid C. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I. Mol Cell Biochem. 2011 Feb;348(1-2):33-42. doi: 10.1007/s11010-010-0634-z. Epub, 2010 Nov 13. PMID:21076856 doi:10.1007/s11010-010-0634-z
- ↑ Marx UC, Adermann K, Bayer P, Meyer M, Forssmann WG, Rosch P. Structure-activity relation of NH2-terminal human parathyroid hormone fragments. J Biol Chem. 1998 Feb 20;273(8):4308-16. PMID:9468478
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