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3fit

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FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) IN COMPLEX WITH ADENOSINE/SULFATE AMP ANALOG

Structural highlights

3fit is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FHIT_HUMAN Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.^[1] Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.^[2]

Function

FHIT_HUMAN Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.^[3]

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

BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a gene located at a fragile site on human chromosome 3, which is commonly disrupted in association with certain cancers. On the basis of the genetic evidence, it has been postulated that the FHIT protein may function as a tumor suppressor, implying a role for the FHIT protein in carcinogenesis. The FHIT protein has dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its role in vivo may involve the hydrolysis of a phosphoanhydride bond. The structural analysis of FHIT will identify critical residues involved in substrate binding and catalysis, and will provide insights into the in vivo function of HIT proteins. RESULTS: The three-dimensional crystal structures of free and nucleoside complexed FHIT have been determined from multiwavelength anomalous diffraction (MAD) data, and they represent some of the first successful structures to be measured with undulator radiation at the Advanced Photon Source. The structures of FHIT reveal that this protein exists as an intimate homodimer, which is based on a core structure observed previously in another human HIT homolog, protein kinase C interacting protein (PKCI), but has distinctive elaborations at both the N and C termini. Conserved residues within the HIT family, which are involved in the interactions of the proteins with nucleoside and phosphate groups, appear to be relevant for the catalytic activity of this protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family member, in complex with a nucleotide analog suggests a metal-independent catalytic mechanism for the HIT family of proteins. A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins.

MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family.,Lima CD, D'Amico KL, Naday I, Rosenbaum G, Westbrook EM, Hendrickson WA Structure. 1997 Jun 15;5(6):763-74. PMID:9261067^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pekarsky Y, Garrison PN, Palamarchuk A, Zanesi N, Aqeilan RI, Huebner K, Barnes LD, Croce CM. Fhit is a physiological target of the protein kinase Src. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3775-9. Epub 2004 Mar 8. PMID:15007172 doi:10.1073/pnas.0400481101
↑ Pekarsky Y, Garrison PN, Palamarchuk A, Zanesi N, Aqeilan RI, Huebner K, Barnes LD, Croce CM. Fhit is a physiological target of the protein kinase Src. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3775-9. Epub 2004 Mar 8. PMID:15007172 doi:10.1073/pnas.0400481101
↑ Barnes LD, Garrison PN, Siprashvili Z, Guranowski A, Robinson AK, Ingram SW, Croce CM, Ohta M, Huebner K. Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5"'-P1,P3-triphosphate hydrolase. Biochemistry. 1996 Sep 10;35(36):11529-35. PMID:8794732 doi:10.1021/bi961415t
↑ Lima CD, D'Amico KL, Naday I, Rosenbaum G, Westbrook EM, Hendrickson WA. MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family. Structure. 1997 Jun 15;5(6):763-74. PMID:9261067

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3fit"

@@ Line 1: / Line 1: @@
 ==FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) IN COMPLEX WITH ADENOSINE/SULFATE AMP ANALOG==
-<StructureSection load='3fit' size='340' side='right' caption='[[3fit]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='3fit' size='340' side='right'caption='[[3fit]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3fit]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FIT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3fit]] 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=3FIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FIT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FHIT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3fit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fit OCA], [https://pdbe.org/3fit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fit RCSB], [https://www.ebi.ac.uk/pdbsum/3fit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fit ProSAT]</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=3fit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fit OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fit RCSB], [http://www.ebi.ac.uk/pdbsum/3fit PDBsum]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN]] Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.<ref>PMID:15007172</ref>   Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.<ref>PMID:15007172</ref>
+[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.<ref>PMID:15007172</ref>   Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.<ref>PMID:15007172</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN]] Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.<ref>PMID:8794732</ref>
+[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.<ref>PMID:8794732</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/fi/3fit_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fi/3fit_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].
+</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/main_output.php?pdb_ID=3fit ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3fit" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Histidine triad nucleotide-binding protein|Histidine triad nucleotide-binding protein]]
+*[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]]
 == References ==
 <references/>
@@ Line 38: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Amico, K L.D]]
+[[Category: Large Structures]]
-[[Category: Hendrickson, W A]]
+[[Category: D'Amico KL]]
-[[Category: Lima, C D]]
+[[Category: Hendrickson WA]]
-[[Category: Naday, I]]
+[[Category: Lima CD]]
-[[Category: Rosenbaum, G]]
+[[Category: Naday I]]
-[[Category: Westbrook, E M]]
+[[Category: Rosenbaum G]]
-[[Category: Advanced photon source]]
+[[Category: Westbrook EM]]
-[[Category: Ap]]
-[[Category: Fhit]]
-[[Category: Fragile histidine triad protein]]
-[[Category: Hit protein family]]
-[[Category: Pkci]]
-[[Category: Putative human tumor suppressor]]

3fit

From Proteopedia

Current revision

FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) IN COMPLEX WITH ADENOSINE/SULFATE AMP ANALOG

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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