IP Library › Granted Patent US 7,071,307
Granted Patent B2
US 7,071,307 · App. 10/141,531 · Granted Jul 4, 2006

Nucleic acids and proteins with thioredoxin reductase activity

Assignees: Syngenta Participations AG; Xencor, Inc.
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Quick Facts
Patent No.
US 7,071,307
App. No.
10/141,531
Granted
Jul 4, 2006
Kind
B2
Abstract

The present invention relates to the use of a variety of methods for generating functional thioredoxin reductase variants in which at least one physical, chemical or biological property of the variant is altered in a specific and desired manner when compared to the wild-type protein.

Claims (103)

1. A variant thioredoxin reductase (TR) protein with altered cofactor specificity as compared to a naturally occurring thioredoxin reductase protein comprising an isolated polypeptide molecule having the formula:

S1-A1-A2-S2-A3-A4-A5-S3-A6-S4

wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid is the amino acid alanine;

g) A3 is the amino acid is the amino acid histidine;

h) A4 is an amino acid moiety selected from the group consisting of arginine and tryptophan;

i) A5 is an amino acid moiety selected from the group consisting of arginine, valine, leucine, isoleucine, methionine, phenylalanine, and tyrosine;

j) A6 is an amino acid moiety selected from the group consisting of arginine, glycine, asparagine, glutamine, serine, and threonine, wherein only zero, one, or two of A4, A5 or A6 are arginine.

2. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

A5 is the amino acid valine; and

A6 is the amino acid arginine.

3. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid methionine; and

j) A6 is the amino acid glycine.

4. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid isoleucine; and

j) A6 is the amino acid serine.

5. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid methionine; and

j) A6 is the amino acid serine.

6. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NQ:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid leucine; and

j) A6 is the amino acid serine.

7. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid arginine; and

j) A6 is the amino acid threonine.

8. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid tryptophan;

i) A5 is the amino acid valine; and

j) A6 is the amino acid glycine.

9. A variant thioredoxin reductase (TR) protein according to claim 1 wherein

a) S1 comprises SEQ ID NO:6;

b) S2 comprises SEQ ID NO:13;

c) S3 comprises SEQ ID NO:20;

d) S4 comprises SEQ ID NO:27;

e) A1 is the amino acid serine;

f) A2 is the amino acid alanine;

g) A3 is the amino acid histidine;

h) A4 is the amino acid arginine;

i) A5 is the amino acid tyrosine; and

j) A6 is the amino acid asparagine.

10. The polypeptide molecule according to any one of claims 1 – 9 , wherein said co-factor towards NADH is altered.

11. The polypeptide molecule according to any one of claims 1 – 9 , wherein said co-factor towards NADPH is altered.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 13, 2007
From: XENCOR
To: XENCOR, INC.
Reel/Frame 019419/0426 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2003
From: DESJARLAIS, JOHN R.; MUCHHAL, UMESH
To: XENCOR
Reel/Frame 013803/0166 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2003
From: DALMIA, BIPIN K.; BRIGGS, STEVEN P.; DEL VAL, GREG; HEIFETZ, PETER; LUGINBUHL, PETER
To: SYNGENTA PARTICIPATIONS AG
Reel/Frame 013655/0323 →
Continuity (4)
Provisional Application 6028902900 · May 4, 2001
Provisional Application 6037060900 · Apr 5, 2002
Provisional Application 6037668200 · Apr 29, 2002
Related Publication 20030100743A1 · May 29, 2003