| Position | Mutant | Location | Description | Notes | References |
|---|---|---|---|---|---|
| 55 | P55G | β2–β3 | no RH; significant DNAP | may reposition P-T so does not contact RH site | 3 |
| 74 | L74V | β4 | contacts template strand beyond DNAP active site | isolated as conferring resistance to ddI in clinical isolates | 5 |
| 89 | E89G | β5a | probably repositions P-T | isolated as ddG-resistant in vitro | 5,14 |
| 100 | L100S | β5b–β6 | no DNAP, little RH, defective in P-T binding | hydrophobic core of palm | 4 |
| 109 | L109S | β6 | minimal DNAP, no RH, defective in P-T binding | hydrophobic core of palm; may alter active site geometry | 4 |
| 110 | D110G | β6 | undetectable DNAP | DNPA catalytic residue | 11 |
| D110E | β6 | no DNAP, RH normal | DNAP catalytic residue | 1 | |
| 111 | V111S | β6 | very low DNAP; RH near normal | hydrophobic core of palm | 4 |
| 113 | D113G | β6–αC | >50% DNAP; ACTR in vitro; RH unaffected | conserved residue | 2,11 |
| 150 | P150G | β8–αE | no DNAP or RH | — | 3 |
| 152 | G152A | β8–αE | no DNAP; WT RH | — | 4 |
| 156 | S156A | αE | no RH; DNAP slightly impaired | may alter position of P-T so does not contact RH site | 3 |
| S156T | no DNAP; RH WT | may alter position of P-T to alter contact with DNAP site | 4 | ||
| S156G | reduced DNAP; RH WT | may alter position of P-T to alter contact with DNAP site | 4 | ||
| 172 | R172S | αE | very low DNAP; RH WT | — | 6 |
| 185 | D185H | β9–β10 | DNAP inactive | DNAP catalytic residue | 11 |
| D185N | DNAP inactive; binds P-T | DNAP catalytic residue | 12 | ||
| D185E | |||||
| 186 | D186N | β10 | DNAP inactive; binds P-T | DNAP catalytic residue | 12 |
| 191 | S191A | β10 | DNAP inactive; mutationally sensitive position | does not fold correctly | 6 |
| 198 | H198R | αF | DNAP inactive; mutationally sensitive position | does not fold correctly; residue conserved among lentiviruses | 6 |
| 229 | W229A | β12 | impaired P-T binding; v. noninfectious | “primer grip” region | 10 |
| 258 | Q258A | αH | WT important to P-T binding | — | 1 |
| 262 | G262A | αH | reduced fidelity DNAP | WT important to P-T binding | 1 |
| 263 | K263S | αH | like WT | crosslinking had suggested binds dNTPs | 13 |
| 266 | W266A | αH | reduced fidelity DNAP | WT important to P-T binding | 1 |
| 289 | L289K | αi–αJ | WT required in p66 for dimerization | — | 9 |
| 443 | D443N | RH | defective RH, some defects in DNAP | RH catalytic residue | 8 |
| 475 | Q475E | RH | defective RH endonuclease activity and PPT cleavage | — | 17 |
| 478 | E478A | RH | RH drastically impaired; DNAP normal | RH catalytic residue | 15 |
| 494 | N494D | RH | resembles WT | conserved residue | 17 |
| 498 | D498N | RH | defective RH and strand transfer; some DNAP defects | RH catalytic residue; protein unstable in absence of D443N | 7,8 |
| 539 | H539F | RH | RH reduced; DNAP normal | conserved residue | 15 |
| H39N | RH thermolabile; DNAP approximately normal; v. noninfectious | conserved residue | 16 | ||
| H539D | RH and DNAP impaired; v. noninfectious | conserved residue | 16 |
All mutant names used standard one-letter amino acid designations with the first letter corresponding to the residue naturally present, the number referring to the amino acid residue affects, and the final letter referring to the mutant amino acid residue. For some mutants, at least some component of the phenotype listed here is conjectural as described in the citations. Abbreviations are as follows: (P-T) primer-template; (WT) wild type; (RH) RNaseH activity; (DNAP) DNA polymerase activity; (v.) in virus. Except where description in virus is provided, all information refers to enzyme properties in purified reactions in vitro.
References: (1) Beard et al. 1994; (2) Boyer et al. 1994a; (3) Boyer et al. 1992a; (4) Boyer et al. 1992b; (5) Boyer et al. 1994c: (6) Chao et al. (1995); (7) DeStefano et al. 1994b; (8) Dudding et al. 1991; (9) Goel et al. 1993; (10) Jacques et al. 1994; (11) Larder et al. 1987; (12) Lowe et al. 1991; (13) Martin et al. 1993; (14) Prasad et al. 1991; (15) Schatz et al. 1989; (16) Tisdale et al. 1991; (17) Volkmann et al. 1993.
From: Biochemistry of Reverse Transcription
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