Abstract
The transition state for the Trypanosoma cruzi uridine phosphorylase (TcUP) reaction has an expanded SN2 character. We used binding isotope effects (BIE's) to probe uridine distortion in the complex with TcUP and sulfate to mimic the Michaelis complex. Inverse 1'-3H and 5'- 3H BIE's indicate a constrained bonding environment of these groups in the complex. Quantum chemical modeling identified a uridine conformer whose calculated BIE's match the experimental values. This conformer differs in sugar pucker and uracil orientation from the unbound conformer and the transition-state structure. These results support ground-state stabilization in the Michaelis complex.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6715-6717 |
| Number of pages | 3 |
| Journal | Biochemistry |
| Volume | 51 |
| Issue number | 34 |
| DOIs | |
| State | Published - Aug 28 2012 |
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ASJC Scopus subject areas
- Biochemistry
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Constrained Bonding Environment in the Michaelis Complex of Trypanosoma cruzi Uridine Phosphorylase. / Silva, Rafael G.; Kipp, D. Randal; Schramm, Vern L.
In: Biochemistry, Vol. 51, No. 34, 28.08.2012, p. 6715-6717.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Constrained Bonding Environment in the Michaelis Complex of Trypanosoma cruzi Uridine Phosphorylase
AU - Silva, Rafael G.
AU - Kipp, D. Randal
AU - Schramm, Vern L.
PY - 2012/8/28
Y1 - 2012/8/28
N2 - The transition state for the Trypanosoma cruzi uridine phosphorylase (TcUP) reaction has an expanded SN2 character. We used binding isotope effects (BIE's) to probe uridine distortion in the complex with TcUP and sulfate to mimic the Michaelis complex. Inverse 1'-3H and 5'- 3H BIE's indicate a constrained bonding environment of these groups in the complex. Quantum chemical modeling identified a uridine conformer whose calculated BIE's match the experimental values. This conformer differs in sugar pucker and uracil orientation from the unbound conformer and the transition-state structure. These results support ground-state stabilization in the Michaelis complex.
AB - The transition state for the Trypanosoma cruzi uridine phosphorylase (TcUP) reaction has an expanded SN2 character. We used binding isotope effects (BIE's) to probe uridine distortion in the complex with TcUP and sulfate to mimic the Michaelis complex. Inverse 1'-3H and 5'- 3H BIE's indicate a constrained bonding environment of these groups in the complex. Quantum chemical modeling identified a uridine conformer whose calculated BIE's match the experimental values. This conformer differs in sugar pucker and uracil orientation from the unbound conformer and the transition-state structure. These results support ground-state stabilization in the Michaelis complex.
UR - http://www.scopus.com/inward/record.url?scp=84867513134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867513134&partnerID=8YFLogxK
U2 - 10.1021/bi300914
DO - 10.1021/bi300914
M3 - Article
C2 - 22870934
AN - SCOPUS:84867513134
VL - 51
SP - 6715
EP - 6717
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 34
ER -