4d1b: Difference between revisions
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''' | ==STRUCTURE OF MHP1, A NUCLEOBASE-CATION-SYMPORT-1 FAMILY TRANSPORTER, IN A CLOSED CONFORMATION WITH BENZYL-HYDANTOIN== | ||
<StructureSection load='4d1b' size='340' side='right' caption='[[4d1b]], [[Resolution|resolution]] 3.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4d1b]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2jlo 2jlo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D1B FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5FH:(5S)-5-BENZYLIMIDAZOLIDINE-2,4-DIONE'>5FH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d1a|4d1a]], [[4d1c|4d1c]], [[4d1d|4d1d]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d1b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d1b RCSB], [http://www.ebi.ac.uk/pdbsum/4d1b PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. | |||
Molecular mechanism of ligand recognition by membrane transport protein, Mhp1.,Simmons KJ, Jackson SM, Brueckner F, Patching SG, Beckstein O, Ivanova E, Geng T, Weyand S, Drew D, Lanigan J, Sharples DJ, Sansom MS, Iwata S, Fishwick CW, Johnson AP, Cameron AD, Henderson PJ EMBO J. 2014 Jun 21. pii: e201387557. PMID:24952894<ref>PMID:24952894</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Brueckner, F.]] | |||
[[Category: Cameron, A D.]] | |||
[[Category: Drew, D.]] | |||
[[Category: Geng, T.]] | |||
[[Category: Henderson, P J.F.]] | |||
[[Category: Iwata, S.]] | |||
[[Category: Weyand, S.]] | |||
[[Category: Membrane protein transporter]] | |||
[[Category: Occluded state]] | |||
[[Category: Substrate-bound]] | |||
[[Category: Transport protein]] | |||
Revision as of 11:20, 2 July 2014
STRUCTURE OF MHP1, A NUCLEOBASE-CATION-SYMPORT-1 FAMILY TRANSPORTER, IN A CLOSED CONFORMATION WITH BENZYL-HYDANTOINSTRUCTURE OF MHP1, A NUCLEOBASE-CATION-SYMPORT-1 FAMILY TRANSPORTER, IN A CLOSED CONFORMATION WITH BENZYL-HYDANTOIN
Structural highlights
Publication Abstract from PubMedThe hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. Molecular mechanism of ligand recognition by membrane transport protein, Mhp1.,Simmons KJ, Jackson SM, Brueckner F, Patching SG, Beckstein O, Ivanova E, Geng T, Weyand S, Drew D, Lanigan J, Sharples DJ, Sansom MS, Iwata S, Fishwick CW, Johnson AP, Cameron AD, Henderson PJ EMBO J. 2014 Jun 21. pii: e201387557. PMID:24952894[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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