2fhi

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[[Image:2fhi.gif|left|200px]]
[[Image:2fhi.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2fhi |SIZE=350|CAPTION= <scene name='initialview01'>2fhi</scene>, resolution 2.60&Aring;
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The line below this paragraph, containing "STRUCTURE_2fhi", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=HIT:The+HIS+Triad+Site+Contains+The+Motif+Common+To+Proteins+...'>HIT</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=IB2:P1-P2-METHYLENE-P3-THIO-DIADENOSINE+TRIPHOSPHATE'>IB2</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Bis(5'-adenosyl)-triphosphatase Bis(5'-adenosyl)-triphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.29 3.6.1.29] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= FHIT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_2fhi| PDB=2fhi | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fhi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fhi OCA], [http://www.ebi.ac.uk/pdbsum/2fhi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fhi RCSB]</span>
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}}
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'''SUBSTRATE ANALOG (IB2) COMPLEX WITH THE HIS 96 ASN SUBSTITUTION OF THE FRAGILE HISTIDINE TRIAD PROTEIN, FHIT'''
'''SUBSTRATE ANALOG (IB2) COMPLEX WITH THE HIS 96 ASN SUBSTITUTION OF THE FRAGILE HISTIDINE TRIAD PROTEIN, FHIT'''
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==Reference==
==Reference==
Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit., Pace HC, Garrison PN, Robinson AK, Barnes LD, Draganescu A, Rosler A, Blackburn GM, Siprashvili Z, Croce CM, Huebner K, Brenner C, Proc Natl Acad Sci U S A. 1998 May 12;95(10):5484-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9576908 9576908]
Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit., Pace HC, Garrison PN, Robinson AK, Barnes LD, Draganescu A, Rosler A, Blackburn GM, Siprashvili Z, Croce CM, Huebner K, Brenner C, Proc Natl Acad Sci U S A. 1998 May 12;95(10):5484-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9576908 9576908]
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[[Category: Bis(5'-adenosyl)-triphosphatase]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Rosler, A.]]
[[Category: Rosler, A.]]
[[Category: Siprashvili, Z.]]
[[Category: Siprashvili, Z.]]
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[[Category: active site substitution]]
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[[Category: Active site substitution]]
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[[Category: cancer]]
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[[Category: Cancer]]
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[[Category: diadenosine triphosphate hydrolase]]
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[[Category: Diadenosine triphosphate hydrolase]]
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[[Category: histidine triad]]
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[[Category: Histidine triad]]
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[[Category: nucleotide-binding protein]]
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[[Category: Nucleotide-binding protein]]
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[[Category: tumor suppressor]]
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[[Category: Tumor suppressor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:54:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:02:51 2008''
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Revision as of 00:54, 4 May 2008

Image:2fhi.gif

Template:STRUCTURE 2fhi

SUBSTRATE ANALOG (IB2) COMPLEX WITH THE HIS 96 ASN SUBSTITUTION OF THE FRAGILE HISTIDINE TRIAD PROTEIN, FHIT


Overview

Alterations in the FHIT gene at 3p14.2 occur as early and frequent events in the development of several common human cancers. The ability of human Fhit-negative cells to form tumors in nude mice is suppressed by stable reexpression of Fhit protein. Fhit protein is a diadenosine P1,P3-triphosphate (ApppA) hydrolase whose fungal and animal homologs form a branch of the histidine triad (HIT) superfamily of nucleotide-binding proteins. Because the His-96 --> Asn substitution of Fhit, which retards ApppA hydrolase activity by seven orders of magnitude, did not block tumor-suppressor activity in vivo, we determined whether this mutation affected ApppA binding or particular steps in the ApppA catalytic cycle. Evidence is presented that His-96 --> Asn protein binds ApppA well and forms an enzyme-AMP intermediate extremely poorly, suggesting that Fhit-substrate complexes are the likely signaling form of the enzyme. The cocrystal structure of Fhit bound to Ado-p-CH2-p-ps-Ado (IB2), a nonhydrolyzable ApppA analog, was refined to 3.1 A, and the structure of His-96 --> Asn Fhit with IB2 was refined to 2.6 A, revealing that two ApppA molecules bind per Fhit dimer; identifying two additional adenosine-binding sites on the dimer surface; and illustrating that His-98 is positioned to donate a hydrogen bond to the scissile bridging oxygen of ApppA substrates. The form of Fhit bound to two ApppA substrates would present to the cell a dramatically phosphorylated surface, prominently displaying six phosphate groups and two adenosine moieties in place of a deep cavity lined with histidines, arginines, and glutamines.

About this Structure

2FHI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit., Pace HC, Garrison PN, Robinson AK, Barnes LD, Draganescu A, Rosler A, Blackburn GM, Siprashvili Z, Croce CM, Huebner K, Brenner C, Proc Natl Acad Sci U S A. 1998 May 12;95(10):5484-9. PMID:9576908 Page seeded by OCA on Sun May 4 03:54:15 2008

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