1bzm: Difference between revisions

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New page: left|200px<br /> <applet load="1bzm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bzm, resolution 2.0Å" /> '''DRUG-PROTEIN INTERAC...
 
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[[Image:1bzm.gif|left|200px]]<br />
<applet load="1bzm" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1bzm, resolution 2.0&Aring;" />
'''DRUG-PROTEIN INTERACTIONS: STRUCTURE OF SULFONAMIDE DRUG COMPLEXED WITH HUMAN CARBONIC ANHYDRASE I'''<br />


==Overview==
==DRUG-PROTEIN INTERACTIONS: STRUCTURE OF SULFONAMIDE DRUG COMPLEXED WITH HUMAN CARBONIC ANHYDRASE I==
N-unsubstituted sulfonamide drugs are widely used for opthalmic disorders., Inhibition of carbonic anhydrase enzyme is believed to be the chief reason, for their therapeutic effects. Structures of three such sulfonamide drugs, complexed to human carbonic anhydrase I enzyme (HCAI) refined, crystallographically at 2 A resolution are reported here. The drug, molecules are all bound in the active site of the enzyme, but among, themselves show differences in the orientations of the sulfamido groups, interacting with the essential zinc ion in the active site. The activity, linked solvent molecule coordinated to zinc in the native enzyme is, displaced by all the three sulfonamides. The active site loop of Leu198, Thr199 and His200 has been identified to be important for binding of the, drug molecules due to their appreciable atomic displacements and, intra-molecular hydrogen bonds arising out of their interactions with the, sulfonamides. These interactions along with active site charge, requirements are proposed to be responsible for the orientational, differences of the sulfamido groups and also for differences in the, inhibitory powers of the drugs. A hydrogen bond network involving solvent, molecules and active site residues His200 and His67 amongst others in the, native enzyme, is disrupted upon binding of methazolamide but not in the, other two sulfonamides. This is the first crystallographic evidence of the, possible involvement of His200 in the inhibition of HCAI. An important, role of Thr199 in distinguishing between the substrate and inhibitor, binding modes of HCO3- to the enzyme at high pH is also inferred.
<StructureSection load='1bzm' size='340' side='right'caption='[[1bzm]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1bzm]] 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=1BZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BZM 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=MZM:N-(3-METHYL-5-SULFAMOYL-1,3,4-THIADIAZOL-2(3H)-YLIDENE)ACETAMIDE'>MZM</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=1bzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bzm OCA], [https://pdbe.org/1bzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bzm RCSB], [https://www.ebi.ac.uk/pdbsum/1bzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bzm 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/bz/1bzm_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=1bzm ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1BZM 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 MZM 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=1BZM OCA].
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 
== References ==
==Reference==
<references/>
Drug-protein interactions. Refined structures of three sulfonamide drug complexes of human carbonic anhydrase I enzyme., Chakravarty S, Kannan KK, J Mol Biol. 1994 Oct 21;243(2):298-309. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7932756 7932756]
__TOC__
[[Category: Carbonate dehydratase]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chakravarty, S.]]
[[Category: Chakravarty S]]
[[Category: Kannan, K.K.]]
[[Category: Kannan KK]]
[[Category: MZM]]
[[Category: ZN]]
[[Category: oxo-acid lyase]]
[[Category: protein-drug interactions]]
[[Category: sulfonamides]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:16:11 2007''

Latest revision as of 09:40, 7 February 2024

DRUG-PROTEIN INTERACTIONS: STRUCTURE OF SULFONAMIDE DRUG COMPLEXED WITH HUMAN CARBONIC ANHYDRASE IDRUG-PROTEIN INTERACTIONS: STRUCTURE OF SULFONAMIDE DRUG COMPLEXED WITH HUMAN CARBONIC ANHYDRASE I

Structural highlights

1bzm 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 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.

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

1bzm, resolution 2.00Å

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