The Anthrax Toxin

The Anthrax Toxin
Bálint Miklós
Geometric Computations in Molecular Biology
May 16th, 2007 - ETH Zurich
Anthrax, the disease
• Infectious disease, mostly animals
• One documented case for domestic pets in
the USA for the last 15 years
• First anthrax vaccine in 1881
Anthrax, the danger
• Fatal in 95% of cases even if treated
• 100 kg of anthrax sprayed on a major city
could kill more than 3,000,000 people
• First-year college knowledge + minimal
equipment = anthrax spores
The quarantined island
Image courtesy of www.hgstump.de
2001 anthrax attacks
Image courtesy of www.wikipedia.com
How does it work?
Bacilus anthracis produces 3 different toxins
Lethal combination
Protective antigen Edema factor
Lethal factor
Lethal combination
MolProbity Ramachandran analysis
MolProbity Ramachandran analysis
MolProbity Ramachandr
1acc.pdb, model 1
1k93.pdb, model 1
General case
180
1jky.pdb, model 1
Glycine
General
case
180180
General Glycine
case
180
180
B 713 SER
180
A B
655 8SER
VAL
A 522 GLN
A 350
A 117
HISSER
C 675 ASN
A 286 SER
439ASP
GLU
AA531
A 746 SER
A 489 ASN
Psi
B 694 VAL
PsiPsi
E 93 ASP
708THR
ALA
CB787
A 510
510 GLN
GLN
C
0
0 0
354 THR
Psi
A 294 ASP
Psi
A 388 ILE
A 398 LEU
A 460 ASN
A
89
A
33 THR
GLU
GLU
A 37 LYS
A 164 ASN
AA258
154
ILE
265
LEU
A
641
GLU
A
151
ILE
A
593
SER
A
174
70
VAL
LEU
0
B 460 GLY
A 170 PHE
459 ASP
B 12 A
LEU
A 389 ASN
AA443
A A539
GLU
731
THR
399ILE
ILE A 590 ARG
A 508AASP
A
LYS
516 ASN
A 558
267
ARG
A 382
ASP
B
571
GLY
A 250 GLN
A
99 GLU
AA 187
ASP
A 326 SER
224
456
TYR
ASP
A 745 HIS
AA 255
B 537 GLY
253SER
ASN
AAA762
THR
A
38
GLU
74
TYR
392
LEU
B 4 ARG
A A55234
LYS
GLN
A 652 GLN
A
115
HIS
B
11 ALA
A
246
ALYS
599
LYSALA
AA
473
276
GLN
A 647 ASP
C 677 GLY
203 VAL
AASN
159 A
ILE
A 758
AA
233
LEU
A
114
LEU
646
LYS
GLN
A 427 ILE
A572
169
LYS
A 324 ILE
A 245AASP
A 285 LEU
426 SER
A 381 LEU
0
B 566 TYR
D 74
E
F
74 ARG
ARG
A
299
GLU
CB
299
GLU
299
GLU
B 526 GLN
A 741
C
ILE
VAL
A C783
THR
B694
544
SER
B 651 LYS
A 298 GLY
-180
-180
-180
0
Proline
Phi
-180
-180
-180
180
180
180180
Psi
PsiPsi
0
A
A 494
199 LEU
THR
A 207 GLU
A 738 SER
C
-180
Psi
A 723 SER
B 702 SER
B 515 LYS
713 ASN
A 119 VAL
A A70597SER
LEU
A 183 SER
A 664 ARG
0
0
Phi Phi
Proline
Pre-proline
180 180
A 730 ARG
-180
-180
-180
-180
0
0
Phi
Phi
180
180
-180
Proline Pre-proline
180
180
180
Psi
Psi
Psi
124 ASN
0
Protective antigen Edema factor
0
0
C 520 PRO
Lethal factor
0
0
A 671 PRO
A 367 PRO
A 238 PRO
A 198 PRO
B 519 THR
0
The killing machine
Protective antigen
Protective antigen
Intrusion
The killing machine
The distruction, part one
The distruction, part two
The distruction, part two
In the end
• There are open questions:
• refolding after translocation
• does LF target other molecules
• But it is clear, it is a very effective killing
machine
Should we be afraid?
• More than 15,000 anthrax hoaxes between
September 2001 and August 2002
• The U.S. Postal Service delivers 107 billion
pieces of First Class mail to 240 million
adults.
• One known case of mailing 5-7 letters
containing pathogenic Bacillus anthracis
Happy end
• Statistically the odds of your next mail to
contain anthrax is virtually zero.