• Something wrong with this record ?

Substrate Specificity, Inhibitor Selectivity and Structure-Function Relationships of Aldo-Keto Reductase 1B15: A Novel Human Retinaldehyde Reductase

J. Giménez-Dejoz, MH. Kolář, FX. Ruiz, I. Crespo, A. Cousido-Siah, A. Podjarny, OA. Barski, J. Fanfrlík, X. Parés, J. Farrés, S. Porté,

. 2015 ; 10 (7) : e0134506. [pub] 20150729

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc16020468

Human aldo-keto reductase 1B15 (AKR1B15) is a newly discovered enzyme which shares 92% amino acid sequence identity with AKR1B10. While AKR1B10 is a well characterized enzyme with high retinaldehyde reductase activity, involved in the development of several cancer types, the enzymatic activity and physiological role of AKR1B15 are still poorly known. Here, the purified recombinant enzyme has been subjected to substrate specificity characterization, kinetic analysis and inhibitor screening, combined with structural modeling. AKR1B15 is active towards a variety of carbonyl substrates, including retinoids, with lower kcat and Km values than AKR1B10. In contrast to AKR1B10, which strongly prefers all-trans-retinaldehyde, AKR1B15 exhibits superior catalytic efficiency with 9-cis-retinaldehyde, the best substrate found for this enzyme. With ketone and dicarbonyl substrates, AKR1B15 also shows higher catalytic activity than AKR1B10. Several typical AKR inhibitors do not significantly affect AKR1B15 activity. Amino acid substitutions clustered in loops A and C result in a smaller, more hydrophobic and more rigid active site in AKR1B15 compared with the AKR1B10 pocket, consistent with distinct substrate specificity and narrower inhibitor selectivity for AKR1B15.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16020468
003      
CZ-PrNML
005      
20160722120050.0
007      
ta
008      
160722s2015 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1371/journal.pone.0134506 $2 doi
024    7_
$a 10.1371/journal.pone.0134506 $2 doi
035    __
$a (PubMed)26222439
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Giménez-Dejoz, Joan $u Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
245    10
$a Substrate Specificity, Inhibitor Selectivity and Structure-Function Relationships of Aldo-Keto Reductase 1B15: A Novel Human Retinaldehyde Reductase / $c J. Giménez-Dejoz, MH. Kolář, FX. Ruiz, I. Crespo, A. Cousido-Siah, A. Podjarny, OA. Barski, J. Fanfrlík, X. Parés, J. Farrés, S. Porté,
520    9_
$a Human aldo-keto reductase 1B15 (AKR1B15) is a newly discovered enzyme which shares 92% amino acid sequence identity with AKR1B10. While AKR1B10 is a well characterized enzyme with high retinaldehyde reductase activity, involved in the development of several cancer types, the enzymatic activity and physiological role of AKR1B15 are still poorly known. Here, the purified recombinant enzyme has been subjected to substrate specificity characterization, kinetic analysis and inhibitor screening, combined with structural modeling. AKR1B15 is active towards a variety of carbonyl substrates, including retinoids, with lower kcat and Km values than AKR1B10. In contrast to AKR1B10, which strongly prefers all-trans-retinaldehyde, AKR1B15 exhibits superior catalytic efficiency with 9-cis-retinaldehyde, the best substrate found for this enzyme. With ketone and dicarbonyl substrates, AKR1B15 also shows higher catalytic activity than AKR1B10. Several typical AKR inhibitors do not significantly affect AKR1B15 activity. Amino acid substitutions clustered in loops A and C result in a smaller, more hydrophobic and more rigid active site in AKR1B15 compared with the AKR1B10 pocket, consistent with distinct substrate specificity and narrower inhibitor selectivity for AKR1B15.
650    _2
$a aldehydreduktasa $x antagonisté a inhibitory $x genetika $x metabolismus $7 D000449
650    _2
$a sekvence aminokyselin $7 D000595
650    _2
$a substituce aminokyselin $7 D019943
650    _2
$a katalytická doména $x genetika $7 D020134
650    _2
$a inhibitory enzymů $x farmakologie $7 D004791
650    _2
$a lidé $7 D006801
650    _2
$a kinetika $7 D007700
650    _2
$a molekulární modely $7 D008958
650    _2
$a oxidoreduktasy působící na aldehydy nebo donory oxo-skupin $x antagonisté a inhibitory $x genetika $x metabolismus $7 D050837
650    _2
$a konformace proteinů $7 D011487
650    _2
$a rekombinantní proteiny $x genetika $x metabolismus $7 D011994
650    _2
$a retinaldehyd $x metabolismus $7 D012172
650    _2
$a strukturní homologie proteinů $7 D040681
650    _2
$a substrátová specifita $7 D013379
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kolář, Michal H $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Neuroscience and Medicine (INM-9) and Institute for Advanced Simulation (IAS-5), Forschungszentrum Jülich GmbH, Jülich, Germany.
700    1_
$a Ruiz, Francesc X $u Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire-Centre de Biologie Intégrative, CNRS, INSERM, UdS, Illkirch CEDEX, France.
700    1_
$a Crespo, Isidro $u Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
700    1_
$a Cousido-Siah, Alexandra $u Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire-Centre de Biologie Intégrative, CNRS, INSERM, UdS, Illkirch CEDEX, France.
700    1_
$a Podjarny, Alberto $u Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire-Centre de Biologie Intégrative, CNRS, INSERM, UdS, Illkirch CEDEX, France.
700    1_
$a Barski, Oleg A $u Diabetes and Obesity Center, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
700    1_
$a Fanfrlík, Jindřich $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
700    1_
$a Parés, Xavier $u Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
700    1_
$a Farrés, Jaume $u Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
700    1_
$a Porté, Sergio $u Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
773    0_
$w MED00180950 $t PloS one $x 1932-6203 $g Roč. 10, č. 7 (2015), s. e0134506
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26222439 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20160722 $b ABA008
991    __
$a 20160722120304 $b ABA008
999    __
$a ok $b bmc $g 1155138 $s 944996
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 10 $c 7 $d e0134506 $e 20150729 $i 1932-6203 $m PLoS One $n PLoS One $x MED00180950
LZP    __
$a Pubmed-20160722

Find record

Citation metrics

Archiving options