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==Structural and functional analysis of TM XI of the NHE1 isoform of thE NA+/H+ exchanger==
<StructureSection load='2kbv' size='340' side='right'caption='[[2kbv]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kbv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 40 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2kbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbv OCA], [https://pdbe.org/2kbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kbv RCSB], [https://www.ebi.ac.uk/pdbsum/2kbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SL9A1_HUMAN SL9A1_HUMAN] Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.<ref>PMID:8901634</ref> <ref>PMID:11350981</ref> <ref>PMID:15035633</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Na(+)/H(+) exchanger isoform 1 is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammals by extruding an intracellular H(+) in exchange for one extracellular Na(+). We characterized structural and functional aspects of the critical transmembrane (TM) segment XI (residues 449-470) by using cysteine scanning mutagenesis and high resolution NMR. Each residue of TM XI was mutated to cysteine in the background of the cysteine-less protein and the sensitivity to water-soluble sulfhydryl reactive compounds MTSET ((2-(trimethylammonium) ethyl)methanethiosulfonate) and MTSES ((2-sulfonatoethyl) methanethiosulfonate) was determined for those residues with at least moderate activity remaining. Of the residues tested, only proteins with mutations L457C, I461C, and L465C were inhibited by MTSET. The activity of the L465C mutant was almost completely eliminated, whereas that of the L457C and I461C mutants was partially affected. The structure of a peptide representing TM XI (residues Lys(447)-Lys(472)) was determined using high resolution NMR spectroscopy in dodecylphosphocholine micelles. The structure consisted of helical regions between Asp(447)-Tyr(454) and Phe(460)-Lys(471) at the N and C termini of the peptide, respectively, connected by a region with poorly defined, irregular structure consisting of residues Gly(455)-Gly(459). TM XI of NHE1 had a structural similarity to TM XI of the Escherichia coli Na(+)/H(+) exchanger NhaA. The results suggest that TM XI is a discontinuous helix, with residue Leu(465) contributing to the pore.

Structural and functional analysis of transmembrane XI of the NHE1 isoform of the Na+/H+ exchanger.,Lee BL, Li X, Liu Y, Sykes BD, Fliegel L J Biol Chem. 2009 Apr 24;284(17):11546-56. Epub 2009 Jan 28. PMID:19176522<ref>PMID:19176522</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2kbv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fliegel L]]
[[Category: Lee BL]]
[[Category: Li X]]
[[Category: Liu Y]]
[[Category: Sykes BD]]