2it4: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: left|200px<br /> <applet load="2it4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2it4, resolution 2.0Å" /> '''X ray structure of t...
 
No edit summary
 
(19 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2it4.gif|left|200px]]<br />
<applet load="2it4" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2it4, resolution 2.0&Aring;" />
'''X ray structure of the complex between Carbonic Anhydrase I and the phosphonate antiviral drug foscarnet'''<br />


==Overview==
==X ray structure of the complex between Carbonic Anhydrase I and the phosphonate antiviral drug foscarnet==
Foscarnet (phosphonoformate trisodium salt), an antiviral used for the, treatment of HIV and herpes virus infections, also acts as an activator or, inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1)., Interaction of the drug with 11 CA isozymes has been investigated, kinetically, and the X-ray structure of its adduct with isoform I (hCA, I-foscarnet complex) has been resolved. The first CA inhibitor possessing, a phosphonate zinc-binding group is thus evidenced, together with the, factors governing recognition of such small molecules by a metalloenzyme, active site. Foscarnet is also a clear-cut example of modulator of an, enzyme activity which can act either as an activator or inhibitor of a CA, isozyme.
<StructureSection load='2it4' size='340' side='right'caption='[[2it4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2it4]] is a 2 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=2IT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IT4 FirstGlance]. <br>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PPF:PHOSPHONOFORMIC+ACID'>PPF</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=2it4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2it4 OCA], [https://pdbe.org/2it4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2it4 RCSB], [https://www.ebi.ac.uk/pdbsum/2it4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2it4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAH1_HUMAN CAH1_HUMAN] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.<ref>PMID:10550681</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/it/2it4_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/main_output.php?pdb_ID=2it4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug with 11 CA isozymes has been investigated kinetically, and the X-ray structure of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The first CA inhibitor possessing a phosphonate zinc-binding group is thus evidenced, together with the factors governing recognition of such small molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example of modulator of an enzyme activity which can act either as an activator or inhibitor of a CA isozyme.


==About this Structure==
Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I.,Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. PMID:17314045<ref>PMID:17314045</ref>
2IT4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and PPF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IT4 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I., Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT, Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17314045 17314045]
</div>
[[Category: Carbonate dehydratase]]
<div class="pdbe-citations 2it4" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Guerri, A.]]
[[Category: Guerri A]]
[[Category: Innocenti, A.]]
[[Category: Innocenti A]]
[[Category: Scozzafava, A.]]
[[Category: Scozzafava A]]
[[Category: Supuran, C.T.]]
[[Category: Supuran CT]]
[[Category: Temperini, C.]]
[[Category: Temperini C]]
[[Category: PPF]]
[[Category: ZN]]
[[Category: antiviral]]
[[Category: carbonic anhydrase]]
[[Category: crystal stucture]]
[[Category: lyase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:47:31 2007''

Latest revision as of 13:15, 30 August 2023

X ray structure of the complex between Carbonic Anhydrase I and the phosphonate antiviral drug foscarnetX ray structure of the complex between Carbonic Anhydrase I and the phosphonate antiviral drug foscarnet

Structural highlights

2it4 is a 2 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 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAH1_HUMAN Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.[1]

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

Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug with 11 CA isozymes has been investigated kinetically, and the X-ray structure of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The first CA inhibitor possessing a phosphonate zinc-binding group is thus evidenced, together with the factors governing recognition of such small molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example of modulator of an enzyme activity which can act either as an activator or inhibitor of a CA isozyme.

Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I.,Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. PMID:17314045[2]

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

See Also

References

  1. ↑ Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
  2. ↑ Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT. Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. PMID:17314045 doi:10.1016/j.bmcl.2007.01.113

2it4, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2it4&oldid=3852025"