Functional Analysis and Molecular Modeling of a Cloned Urate Transporter/Channel

Functional Analysis and Molecular Modeling of a Cloned Urate Transporter/Channel Recombinant protein, designated UAT, prepared from a cloned rat renal cDNA library functions as a selective voltage-sensitive urate transporter/channel when fused with lipid bilayers. Since we previously suggested that UAT may represent the mammalian electrogenic urate transporter, UAT has been functionally characterized in the presence and absence of potential channel blockers, several of which are known to block mammalian electrogenic urate transport. Two substrates, oxonate (a competitive uricase inhibitor) and pyrazinoate, that inhibit renal electrogenic urate transport also block UAT activity. Of note, oxonate selectively blocks from the cytoplasmic side of the channel while pyrazinoate only blocks from the channel's extracellular face. Like oxonate, anti-uricase (an electrogenic transport inhibitor) also selectively blocks channel activity from the cytoplasmic side. Adenosine blocks from the extracellular side exclusively while xanthine blocks from both sides. These effects are consistent with newly identified regions of homology to uricase and the adenosine A1/A3 receptor in UAT and localize these homologous regions to the cytoplasmic and extracellular faces of UAT, respectively. Additionally, computer analyses identified four putative α-helical transmembrane domains, two β sheets, and blocks of homology to the E and B loops of aquaporin-1 within UAT. The experimental observations substantiate our proposal that UAT is the molecular representation of the renal electrogenic urate transporter and, in conjunction with computer algorithms, suggest a possible molecular structure for this unique channel. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Functional Analysis and Molecular Modeling of a Cloned Urate Transporter/Channel

Loading next page...
 
/lp/springer-journals/functional-analysis-and-molecular-modeling-of-a-cloned-urate-OHBxS3Poi5
Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 1999 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/PL00005897
Publisher site
See Article on Publisher Site

Abstract

Recombinant protein, designated UAT, prepared from a cloned rat renal cDNA library functions as a selective voltage-sensitive urate transporter/channel when fused with lipid bilayers. Since we previously suggested that UAT may represent the mammalian electrogenic urate transporter, UAT has been functionally characterized in the presence and absence of potential channel blockers, several of which are known to block mammalian electrogenic urate transport. Two substrates, oxonate (a competitive uricase inhibitor) and pyrazinoate, that inhibit renal electrogenic urate transport also block UAT activity. Of note, oxonate selectively blocks from the cytoplasmic side of the channel while pyrazinoate only blocks from the channel's extracellular face. Like oxonate, anti-uricase (an electrogenic transport inhibitor) also selectively blocks channel activity from the cytoplasmic side. Adenosine blocks from the extracellular side exclusively while xanthine blocks from both sides. These effects are consistent with newly identified regions of homology to uricase and the adenosine A1/A3 receptor in UAT and localize these homologous regions to the cytoplasmic and extracellular faces of UAT, respectively. Additionally, computer analyses identified four putative α-helical transmembrane domains, two β sheets, and blocks of homology to the E and B loops of aquaporin-1 within UAT. The experimental observations substantiate our proposal that UAT is the molecular representation of the renal electrogenic urate transporter and, in conjunction with computer algorithms, suggest a possible molecular structure for this unique channel.

Journal

The Journal of Membrane BiologySpringer Journals

Published: May 1, 1999

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off