Principles of Bioinorganic Chemistry - 2003
Lecture
1
2
3
4
5
6
7
8
9
10
11
12
13
14
*Makeup
Date
Lecture Topic
Reading
n+
9/4 (Th)
Intro; Choice, Uptake, Assembly of M Ions
Ch. 5
9/ 9 (Tu)
Metalloregulation of Gene Expression
Ch. 6
9/11 (Th)
Metallochaperones; Metal Folding, X-linking
Ch. 7
9/16 (Tu)
Zinc Fingers; Metal Folding; Cisplatin
Ch. 8
9/18 (Th)
Cisplatin; Electron Transfer; Fundamentals
Ch. 9
9/ 23 (Tu)
ET Units; Long-Distance Electron Transfer
Ch. 9
9/25 (Th)
Hydrolytic Enzymes, Zinc, Ni, Co
Ch. 10
10/7 (Tu)
Model Complexes for Metallohydrolases
Ch. 10
10/9 (Th)
Dioxygen Carriers: Hb, Mb, Hc, Hr
Ch. 11
10/14 (Tu)
O2 Activation, Hydroxylation: MMO, P-450, R2 Ch. 11
10/16 (Th)
Model Chemistry for O 2 Carriers/Activators
Ch. 12
10/20 (Mo)* Complex Systems: cyt. oxidase; nitrogenase
Ch. 12
10/21 (Tu)
Metalloneurochemistry/MedicinalInorg. Chem.
10/23 (Th)
Term Examination
class, 5:30 – 7:00 PM.
Problems
Ch. 1
Ch. 2
Ch. 3
Ch. 4
Ch. 5
Ch. 6
Ch. 7
Ch. 8
Ch. 9
Ch. 10
Ch. 11
Ch. 12
The grade for this course will be determined by a term exam (35%), a written research paper
with oral presentation (45%), problem sets (12%) and classroom participation (8%). The oral
presentations will be held in research conference style at MIT's Endicott House estate in
Dedham, MA, on Saturday, October 18. Please reserve the date for there are no excused
absences. Papers will be due approximately one week earlier.
WEB SITE: web.mit.edu/5.062/www/
The Major Metal Units in ET Proteins (1)
Iron-Sulfur
Clusters
Properties of Iron-Sulfur Clusters
(A) Rubredoxin
Fe–S, 2.25 - 2.30 Å in oxidized (FeIII) and reduced (FeII) states
Reduction potentials: - 50 to + 50 mV
(B) 2Fe-2S Ferredoxins (Fd)
FeII FeII
FeII FeIII
reduced
mixed-valent
Reminder:
FeIII FeIII
oxidized
all physiological uses
Reduction potentials: -490 to - 280 mV
(C) 3Fe-4S Ferredoxins (cube missing a corner)
FeIII 3S4
FeIII 2 FeII S4
Reduction potentials: -700 to - 100 mV
eo =
-RT/nF lnQ + pH,
where Q =
[Mn]/[Mn-1]
Thus, at pH 7, the
biological H2/2H+
standard couple
is - 420 mV.
Properties of Iron-Sulfur Clusters, cont’d
(D) 4Fe-4S Ferredoxins and High-potential Iron Proteins (HiPIPs)
The three state hypothesis:
FeII3 FeIII
FeII2 FeIII2
Ferredoxin
FeII FeIII3
HiPIP
Reduction potentials: -650 to - 280 mV (Fd); + 350 mV (HiPIP)
minimal reorganizational energy
The Physical Properties of Iron-Sulfur Clusters
Structure of an 8Fe-8S
Ferredoxin
Primary structure (sequence)
does not dictate the tertiary
structure of a metalloprotein,
as revealed by this 8-iron
ferredoxin crystal structure.
The Major Metal Units in ET Proteins (2)
Blue Copper and CuA
Depicted at the right are the
three copper sites in the enzyme
ascorbate oxidase. Type 1, or
blue, copper is the ET center.
Below is depicted CuA .
His
Glu
Cys
O
S
N
Cu
N
N
Cu
N
S
Blue Copper
S
CuA
Met
Cys
His
The Physical Properties of Blue Copper Centers
The deep sky blue
color of these
proteins facilitated
their purification on
columns; the optical
band is Cu–S C.T.
Structure of Poplar
Plastocyanin
The copper(II) thiolate
center is difficult to
model.
The oxidized, reduced and apo plastocyanin
structures are nearly identical.
EPR Spectra Distinguish the
Three Types of Copper
Found in Metalloproteins
CuA Model Chemistry: Reversible 1-Electron Transfer
His
Glu
Cys
N Cu
N
Me
Cys
Cu
His
3+
Cu
N
N
2.5-2.7
CuA
N
N N
N
N
Cu N
S
S
Met
O
S
Cu-Cu
dist (Å)
2.448
N
N
+
O
O
O
Cu
O
O
2.4246(12)
O
Cu O
LeCloux
O
R
O
Cu
+
O
2.4500(15)
Cu
N
N
N
N
R = Ph3C-
Chuan He
These complexes demonstrate that
constrained dicopper(I/II) units afford
good 1-electron reversible transfer
centers and display the possible
environments that could be
encountered in biology.
The Major Metal Units in ET Proteins (3)
Cytochrome c
from tuna
showing
coordination
of the iron
porphyrin
group by the
protein side
chains from
Met (left) and
His (right)
residues.
Electronic Properties of Low-Spin Metalloporphyrins
COO-
Note again,
minimal
reorganization
energy upon
electron transfer
N
N
Fe
COON
N
protoporphyrin IX
- e-
low spin ferrous
For [Fe(N4-porphyrin)(N-His)(S-Met)]
low spin ferric
Long-Distance Electron Transfer in Proteins
O1
O3
O2
etc
R1
O = oxidized form
R = reduced form
R3
R2
Three ways to measure:
1. Self-exchange
RedAz + OxAz
CuI
OxAz + RedAz
CuII
CuII
k = 1.3 x 106 M-1 s-1
CuI
2. Artificial donor-acceptor pairs
3. Study of natural protein redox pairs
for azurin
Artificial Donor-Acceptor Pairs
Cytochrome c;
Fe---Ru, ~12 Å