Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery
Abstract
:1. Introduction
2. NTCP: Structure and Transport Activity
2.1. NTCP’s Protein Sequence Is Evolutionary Conserved
2.2. Prediction of Human NTCP Structure: Homology and Computational Approaches
2.3. NTCP Primary Function: Bile Acid Uptake
3. Protein Engineering as a Valuable Approach to Study NTCP Functions
Mutation | Functional Consequences | Ref. |
---|---|---|
N5Q |
| [33,34] |
N5A |
| [34] |
N5Q/N11Q |
| [33,34] |
N5A/N11A |
| [34] |
N11Q |
| [33,34] |
N11A |
| [34] |
D24N |
| [66] |
V29I/I38V |
| [13] |
C44A |
| [66] |
C44W |
| [66] |
C44T |
| [66] |
E47Q |
| [66] |
G60L |
| [71,75] |
A64L |
| [71,75] |
Q68A |
| [78] |
K81-S119 (Replacement) | inhibited HBV infection | [9] |
84RLKN87 (Replacement) |
| [9,77,80] |
R84H |
| [77] |
K86T |
| [77,80] |
R84Q/K86N |
| [13] |
N87S |
| [77] |
E89Q |
| [66] |
C96A |
| [66] |
C96W |
| [66] |
C98A |
| [66] |
C98W |
| [66] |
S105A/ N106A |
| [78] |
D115N |
| [66] |
S119A |
| [78] |
120I-S178 (replacement) |
| [9] |
T123A |
| [78] |
C125A |
| [66] |
C125del |
| [66] |
L136A/ L137A |
| [73] |
I140L/S142T |
| [13] |
G144A/G148A |
| [70] |
D147N |
| [66] |
157KGIVISLVL165 (Replacement) |
| [9,13] |
G158R/D/N/V/S |
| [62] |
S162A/ L163A |
| [78] |
C170A |
| [66] |
C170W |
| [66] |
S213A |
| [73] |
T219A |
| [73] |
L222A |
| [67,73] |
I223T |
| [67] |
T225A |
| [73] |
T225A/S226A |
| [73] |
S226A |
| [73] |
S227A |
| [73] |
G233L |
| [71,75] |
G237L |
| [71,75] |
C250A |
| [66] |
C250Del |
| [66] |
R252H |
| [20] |
E257Q |
| [66] |
E257A |
| [78] |
T258A |
| [78] |
C260A |
| [78] |
Q261A |
| [78] |
N262A |
| [78] |
C266A |
| [66] |
C266Del |
| [66] |
S267F |
| [62,67,68,78,79] |
S267/X (X represents 19 aa used in the study) |
| [26] |
F274A |
| [63] |
E277Q |
| [66] |
I279T |
| [67] |
F285A/P286A/L287A |
| [78] |
Q293A/L294A |
| [78] |
I303M/R305W |
| [13] |
C306A |
| [66] |
C306W |
| [66] |
C306Del |
| [66] |
Y307E/K/I Y307Stop |
| [64,65] |
K314E |
| [67] |
T317A |
| [66] |
T317Y |
| [66] |
T320A |
| [66] |
T320Y |
| [66] |
Y321K/A/A |
| [64,65,75] |
4. NTCP: A Promising Target for Drug Discovery against HBV/HDV Infection
5. Conclusions and Future Research
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Zakrzewicz, D.; Geyer, J. Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery. Biomedicines 2022, 10, 196. https://doi.org/10.3390/biomedicines10010196
Zakrzewicz D, Geyer J. Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery. Biomedicines. 2022; 10(1):196. https://doi.org/10.3390/biomedicines10010196
Chicago/Turabian StyleZakrzewicz, Dariusz, and Joachim Geyer. 2022. "Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery" Biomedicines 10, no. 1: 196. https://doi.org/10.3390/biomedicines10010196
APA StyleZakrzewicz, D., & Geyer, J. (2022). Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery. Biomedicines, 10(1), 196. https://doi.org/10.3390/biomedicines10010196