View source for 2wd2


==A chimeric microtubule disruptor with efficacy on a taxane resistant cell line==
<StructureSection load='2wd2' size='340' side='right'caption='[[2wd2]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wd2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WD2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WD2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MS5:7-METHOXY-2-(3-METHOXYBENZYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-6-YL+SULFAMATE'>MS5</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1okl|1okl]], [[1i9q|1i9q]], [[1zfq|1zfq]], [[1if7|1if7]], [[1cam|1cam]], [[1t9n|1t9n]], [[1cnw|1cnw]], [[1okn|1okn]], [[1f2w|1f2w]], [[1g52|1g52]], [[2h4n|2h4n]], [[1bnm|1bnm]], [[1bnq|1bnq]], [[1cnh|1cnh]], [[1ugc|1ugc]], [[1xev|1xev]], [[1ugg|1ugg]], [[1if9|1if9]], [[1g53|1g53]], [[1fqm|1fqm]], [[1ca2|1ca2]], [[1cal|1cal]], [[1fql|1fql]], [[1i9n|1i9n]], [[1g4o|1g4o]], [[2cba|2cba]], [[1ydc|1ydc]], [[1ccs|1ccs]], [[1lzv|1lzv]], [[1bnv|1bnv]], [[1fqr|1fqr]], [[1rzb|1rzb]], [[1a42|1a42]], [[1th9|1th9]], [[1zsb|1zsb]], [[1cnb|1cnb]], [[1hed|1hed]], [[1i8z|1i8z]], [[1g48|1g48]], [[1lg5|1lg5]], [[1g0f|1g0f]], [[1bv3|1bv3]], [[1tg3|1tg3]], [[1cvc|1cvc]], [[1ugd|1ugd]], [[1i90|1i90]], [[1yo0|1yo0]], [[1fsn|1fsn]], [[1hva|1hva]], [[1rze|1rze]], [[1ugb|1ugb]], [[1z9y|1z9y]], [[2fmz|2fmz]], [[1cnk|1cnk]], [[1bn1|1bn1]], [[1teq|1teq]], [[1rza|1rza]], [[2vvb|2vvb]], [[1ccu|1ccu]], [[1i9l|1i9l]], [[2cbc|2cbc]], [[1g46|1g46]], [[1cvb|1cvb]], [[1cao|1cao]], [[1fsq|1fsq]], [[6ca2|6ca2]], [[5ca2|5ca2]], [[1caj|1caj]], [[1g1d|1g1d]], [[1cvf|1cvf]], [[2fou|2fou]], [[1lgd|1lgd]], [[1if6|1if6]], [[1bn4|1bn4]], [[1teu|1teu]], [[1cra|1cra]], [[1ze8|1ze8]], [[1if4|1if4]], [[1hea|1hea]], [[1hca|1hca]], [[1cah|1cah]], [[1g4j|1g4j]], [[1kwq|1kwq]], [[1raz|1raz]], [[1cim|1cim]], [[1cvh|1cvh]], [[1if8|1if8]], [[1cin|1cin]], [[1i9m|1i9m]], [[1zfk|1zfk]], [[1fqn|1fqn]], [[1zsa|1zsa]], [[1lg6|1lg6]], [[1cnc|1cnc]], [[1bnn|1bnn]], [[1uga|1uga]], [[2foq|2foq]], [[1tb0|1tb0]], [[1cai|1cai]], [[1dcb|1dcb]], [[2ax2|2ax2]], [[1cnx|1cnx]], [[5cac|5cac]], [[2hd6|2hd6]], [[4cac|4cac]], [[1ttm|1ttm]], [[1cak|1cak]], [[1i9o|1i9o]], [[1cni|1cni]], [[1can|1can]], [[2eu3|2eu3]], [[1yda|1yda]], [[1eou|1eou]], [[1yo2|1yo2]], [[1mua|1mua]], [[2ca2|2ca2]], [[1cct|1cct]], [[1oq5|1oq5]], [[2abe|2abe]], [[1ugf|1ugf]], [[1rzc|1rzc]], [[2cbe|2cbe]], [[1thk|1thk]], [[1kwr|1kwr]], [[1zgf|1zgf]], [[1cay|1cay]], [[1cng|1cng]], [[1moo|1moo]], [[1hec|1hec]], [[2ez7|2ez7]], [[9ca2|9ca2]], [[1fr7|1fr7]], [[8ca2|8ca2]], [[1zh9|1zh9]], [[1ydd|1ydd]], [[1bic|1bic]], [[1lug|1lug]], [[1caz|1caz]], [[7ca2|7ca2]], [[1cvd|1cvd]], [[1fr4|1fr4]], [[4ca2|4ca2]], [[1cil|1cil]], [[2geh|2geh]], [[1g45|1g45]], [[1ydb|1ydb]], [[1dca|1dca]], [[1fsr|1fsr]], [[2cbb|2cbb]], [[1i9p|1i9p]], [[12ca|12ca]], [[1avn|1avn]], [[1bcd|1bcd]], [[1am6|1am6]], [[1i91|1i91]], [[1cve|1cve]], [[1g3z|1g3z]], [[1heb|1heb]], [[2cbd|2cbd]], [[1zsc|1zsc]], [[3ca2|3ca2]], [[1bnu|1bnu]], [[1zge|1zge]], [[1bnw|1bnw]], [[2fov|2fov]], [[1te3|1te3]], [[1bnt|1bnt]], [[1if5|1if5]], [[1yo1|1yo1]], [[1g54|1g54]], [[1rzd|1rzd]], [[1uge|1uge]], [[1ray|1ray]], [[2fmg|2fmg]], [[1g0e|1g0e]], [[1cva|1cva]], [[1ca3|1ca3]], [[2eu2|2eu2]], [[1tg9|1tg9]], [[1tbt|1tbt]], [[1xeg|1xeg]], [[1bn3|1bn3]], [[1okm|1okm]], [[1cny|1cny]], [[1cnj|1cnj]], [[1h9n|1h9n]], [[2vva|2vva]], [[2aw1|2aw1]], [[1h4n|1h4n]], [[2fos|2fos]], [[1h9q|1h9q]], [[2wd3|2wd3]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wd2 OCA], [http://pdbe.org/2wd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wd2 RCSB], [http://www.ebi.ac.uk/pdbsum/2wd2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wd2 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://omim.org/entry/259730 259730]]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</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/wd/2wd2_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=2wd2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A chimeric approach is used to discover microtubule disruptors with excellent in vitro activity and oral bioavailability; a ligand-protein interaction with carbonic anhydrase that enhances bioavailability is characterised by protein X-ray crystallography. Dosing of a representative chimera in a tumour xenograft model confirms the excellent therapeutic potential of the class.

Chimeric microtubule disruptors.,Leese MP, Jourdan F, Kimberley MR, Cozier GE, Thiyagarajan N, Stengel C, Regis-Lydi S, Foster PA, Newman SP, Acharya KR, Ferrandis E, Purohit A, Reed MJ, Potter BV Chem Commun (Camb). 2010 May 7;46(17):2907-9. Epub 2010 Mar 20. PMID:20386818<ref>PMID:20386818</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2wd2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Acharya, K R]]
[[Category: Cozier, G E]]
[[Category: Ferrandis, E]]
[[Category: Foster, P A]]
[[Category: Jourdan, F L]]
[[Category: Kimberley, M R]]
[[Category: Leese, M P]]
[[Category: Newman, S P]]
[[Category: Potter, B V.L]]
[[Category: Purohit, A]]
[[Category: Reed, M J]]
[[Category: Regis-Lydi, S]]
[[Category: Thiyagarajan, N]]
[[Category: Cancer]]
[[Category: Disease mutation]]
[[Category: Human carbonic anhydrase inhibitor]]
[[Category: Lyase]]
[[Category: Metal-binding]]