Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Crystal structures of Trypanosoma brucei hypoxanthine - guanine - xanthine phosphoribosyltransferase in complex with IMP, GMP and XMP

D. Terán, E. Doleželová, DT. Keough, D. Hocková, A. Zíková, LW. Guddat,

. 2019 ; 286 (23) : 4721-4736. [pub] 20190724

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20023390

Grantová podpora
CZ.02.1.01/0.0/0.0/16_019/0000759 ERD Funds - International
1147368 National Health and Medical Research Council - International
RVO 61388963 Institute of Organic Chemistry and Biochemistry - International
19-07707S Czech Science Foundation - International

E-zdroje Online Plný text

NLK Free Medical Journals od 2005 do Před 1 rokem
Medline Complete (EBSCOhost) od 2005-01-01 do Před 1 rokem
Wiley Free Content od 2005 do Před 1 rokem

The 6-oxopurine phosphoribosyltransferases (PRTs) are drug targets for the treatment of parasitic diseases. This is due to the fact that parasites are auxotrophic for the 6-oxopurine bases relying on salvage enzymes for the synthesis of their 6-oxopurine nucleoside monophosphates. In Trypanosoma brucei, the parasite that is the aetiological agent for sleeping sickness, there are three 6-oxopurine PRT isoforms. Two are specific for hypoxanthine and guanine, whilst the third, characterized here, uses all three naturally occurring bases with similar efficiency. Here, we have determined crystal structures for TbrHGXPRT in complex with GMP, XMP and IMP to investigate the structural basis for substrate specificity. The results show that Y201 and E208, not commonly observed within the purine binding pocket of 6-oxopurine PRTs, contribute to the versatility of this enzyme. The structures further show that a nearby water can act as an adaptor to facilitate the binding of XMP and GMP. When GMP binds, a water can accept a proton from the 2-amino group but when XMP binds, the equivalent water can donate its proton to the 2-oxo group. However, when IMP is bound, no water molecule is observed at that location. DATABASE: Coordinates and structure factors were submitted to the Protein Data Bank and have accession codes of 6MXB, 6MXC, 6MXD and 6MXG for the TbrHGXPRT.XMP complex, TbrHGXPRT.GMP complex, TbrHGXPRT.IMP complex, and TbrHGPRT.XMP complex, respectively.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20023390
003      
CZ-PrNML
005      
20201214125919.0
007      
ta
008      
201125s2019 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1111/febs.14987 $2 doi
035    __
$a (PubMed)31287615
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Terán, David $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
245    10
$a Crystal structures of Trypanosoma brucei hypoxanthine - guanine - xanthine phosphoribosyltransferase in complex with IMP, GMP and XMP / $c D. Terán, E. Doleželová, DT. Keough, D. Hocková, A. Zíková, LW. Guddat,
520    9_
$a The 6-oxopurine phosphoribosyltransferases (PRTs) are drug targets for the treatment of parasitic diseases. This is due to the fact that parasites are auxotrophic for the 6-oxopurine bases relying on salvage enzymes for the synthesis of their 6-oxopurine nucleoside monophosphates. In Trypanosoma brucei, the parasite that is the aetiological agent for sleeping sickness, there are three 6-oxopurine PRT isoforms. Two are specific for hypoxanthine and guanine, whilst the third, characterized here, uses all three naturally occurring bases with similar efficiency. Here, we have determined crystal structures for TbrHGXPRT in complex with GMP, XMP and IMP to investigate the structural basis for substrate specificity. The results show that Y201 and E208, not commonly observed within the purine binding pocket of 6-oxopurine PRTs, contribute to the versatility of this enzyme. The structures further show that a nearby water can act as an adaptor to facilitate the binding of XMP and GMP. When GMP binds, a water can accept a proton from the 2-amino group but when XMP binds, the equivalent water can donate its proton to the 2-oxo group. However, when IMP is bound, no water molecule is observed at that location. DATABASE: Coordinates and structure factors were submitted to the Protein Data Bank and have accession codes of 6MXB, 6MXC, 6MXD and 6MXG for the TbrHGXPRT.XMP complex, TbrHGXPRT.GMP complex, TbrHGXPRT.IMP complex, and TbrHGPRT.XMP complex, respectively.
650    _2
$a sekvence aminokyselin $7 D000595
650    _2
$a kyselina 5'-guanylová $x chemie $x metabolismus $7 D006157
650    _2
$a inosinmonofosfát $x chemie $x metabolismus $7 D007291
650    _2
$a pentosyltransferasy $x chemie $x metabolismus $7 D010430
650    _2
$a konformace proteinů $7 D011487
650    _2
$a ribonukleotidy $x chemie $x metabolismus $7 D012265
650    _2
$a substrátová specifita $7 D013379
650    _2
$a Trypanosoma brucei brucei $x enzymologie $7 D014346
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Doleželová, Eva $u Biology Centre CAS, Institute of Parasitology, České Budějovice, Czech Republic. Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
700    1_
$a Keough, Dianne T $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
700    1_
$a Hocková, Dana $u The Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague 6, Czech Republic.
700    1_
$a Zíková, Alena $u Biology Centre CAS, Institute of Parasitology, České Budějovice, Czech Republic. Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
700    1_
$a Guddat, Luke W $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
773    0_
$w MED00008414 $t The FEBS journal $x 1742-4658 $g Roč. 286, č. 23 (2019), s. 4721-4736
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31287615 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20201214125918 $b ABA008
999    __
$a ok $b bmc $g 1595709 $s 1114066
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 286 $c 23 $d 4721-4736 $e 20190724 $i 1742-4658 $m The FEBS journal $n FEBS J $x MED00008414
GRA    __
$a CZ.02.1.01/0.0/0.0/16_019/0000759 $p ERD Funds $2 International
GRA    __
$a 1147368 $p National Health and Medical Research Council $2 International
GRA    __
$a RVO 61388963 $p Institute of Organic Chemistry and Biochemistry $2 International
GRA    __
$a 19-07707S $p Czech Science Foundation $2 International
LZP    __
$a Pubmed-20201125

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...