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New page: left|200px<br /> <applet load="1itq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1itq, resolution 2.30Å" /> '''HUMAN RENAL DIPEPTI...
 
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[[Image:1itq.gif|left|200px]]<br />
<applet load="1itq" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1itq, resolution 2.30&Aring;" />
'''HUMAN RENAL DIPEPTIDASE'''<br />


==Overview==
==HUMAN RENAL DIPEPTIDASE==
Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing, dipeptides and is involved in hydrolytic metabolism of penem and, carbapenem beta-lactam antibiotics. The crystal structures of the, saccharide-trimmed enzyme are determined as unliganded and, inhibitor-liganded forms. They are informative for designing new, antibiotics that are not hydrolyzed by this enzyme. The active site in, each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is, composed of binuclear zinc ions bridged by the Glu125 side-chain located, at the bottom of the barrel, and it faces toward the microvillar membrane, of a kidney tubule. A dipeptidyl moiety of the therapeutically used, cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The, barrel and active-site architectures utilizing catalytic metal ions, exhibit unexpected similarities to those of the murine adenosine deaminase, and the catalytic domain of the bacterial urease.
<StructureSection load='1itq' size='340' side='right'caption='[[1itq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1itq]] 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=1ITQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ITQ 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1itq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1itq OCA], [https://pdbe.org/1itq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1itq RCSB], [https://www.ebi.ac.uk/pdbsum/1itq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1itq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPEP1_HUMAN DPEP1_HUMAN] Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. Converts leukotriene D4 to leukotriene E4; it may play an important role in the regulation of leukotriene activity.
== 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/1itq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1itq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms. They are informative for designing new antibiotics that are not hydrolyzed by this enzyme. The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease.


==Disease==
Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.,Nitanai Y, Satow Y, Adachi H, Tsujimoto M J Mol Biol. 2002 Aug 9;321(2):177-84. PMID:12144777<ref>PMID:12144777</ref>
Known disease associated with this structure: Dystonia-12 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182350 182350]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1ITQ 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 NAG and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Membrane_dipeptidase Membrane dipeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.13.19 3.4.13.19] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ITQ OCA].
</div>
 
<div class="pdbe-citations 1itq" style="background-color:#fffaf0;"></div>
==Reference==
== References ==
Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis., Nitanai Y, Satow Y, Adachi H, Tsujimoto M, J Mol Biol. 2002 Aug 9;321(2):177-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12144777 12144777]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Membrane dipeptidase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Adachi H]]
[[Category: Adachi, H.]]
[[Category: Nitanai Y]]
[[Category: Nitanai, Y.]]
[[Category: Satow Y]]
[[Category: Satow, Y.]]
[[Category: Tsujimoto M]]
[[Category: Tsujimoto, M.]]
[[Category: NAG]]
[[Category: ZN]]
[[Category: cilastatin]]
[[Category: complex (hydrolase/inhibitor)]]
[[Category: dipeptidase]]
[[Category: glycoprotein]]
[[Category: membrane-bound]]
[[Category: zinc protease beta-lactamase]]
 
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Retrieved from "https://proteopedia.org/1itq"