principles of bioinorganic chemistry - 2003
DESCRIPTION
Principles of Bioinorganic Chemistry - 2003. - PowerPoint PPT PresentationTRANSCRIPT
Principles of Bioinorganic Chemistry - 2003
Lecture Date Lecture Topic Reading Problems1 9/4 (Th) Intro; Choice, Uptake, Assembly of Mn+ Ions Ch. 5 Ch. 12 9/ 9 (Tu) Metalloregulation of Gene Expression Ch. 6 Ch. 23 9/11 (Th) Metallochaperones; Metal Folding, X-linkingCh. 7 Ch. 34 9/16 (Tu) Zinc Fingers; Metal Folding; Cisplatin Ch. 8 Ch. 45 9/18 (Th) Cisplatin; Electron Transfer; Fundamentals Ch. 9 Ch. 56 9/ 23 (Tu) ET Units; Long-Distance Electron TransferCh. 9 Ch. 67 9/25 (Th) Hydrolytic Enzymes, Zinc, Ni, Co Ch. 10 Ch. 78 10/7 (Tu) Model Complexes for Metallohydrolases Ch. 10 Ch. 89 10/9 (Th) Dioxygen Carriers: Hb, Mb, Hc, Hr Ch. 11 Ch. 910 10/14 (Tu) O2 Activation, Hydroxylation: MMO, P-450, R2Ch. 11 Ch. 1011 10/16 (Th) Model Chemistry for O2 Carriers/Activators Ch. 12 Ch. 1112 10/20 (Mo)* Complex Systems: cyt. oxidase; nitrogenase Ch. 12 Ch. 1213 10/21 (Tu) Metalloneurochemistry/Medicinal Inorg. Chem.14 10/23 (Th) Term Examination
*Makeup class, 5:30 – 7:00 PM.
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-SulfurClusters
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 FeIII FeIII
reduced mixed-valent 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
Reminder:
o =-RT/nF lnQ + pH,where Q = [Mn]/[Mn-1]
Thus, at pH 7, the biological H2/2H+
standard coupleis - 420 mV.
Properties of Iron-Sulfur Clusters, cont’d
(D) 4Fe-4S Ferredoxins and High-potential Iron Proteins (HiPIPs)
FeII3
FeIII FeII2
FeIII2 FeII FeIII
3
HiPIP
Reduction potentials: -650 to - 280 mV (Fd); + 350 mV (HiPIP)
The three state hypothesis:
Ferredoxin
minimal reorganizational energy
The Physical Properties of Iron-Sulfur Clusters
Primary structure (sequence) does not dictate the tertiary structure of a metalloprotein, as revealed by this 8-iron ferredoxin crystal structure.
Structure of an 8Fe-8S Ferredoxin
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 .
Blue Copper
SCu
SS
Cu
O
NN
NN
HisGlu
Cys
HisMet CysCuA
The Physical Properties of Blue Copper Centers
The deep sky bluecolor of theseproteins facilitated their purification on columns; the opticalband is Cu–S C.T.
Structure of Poplar Plastocyanin
The oxidized, reduced and apo plastocyanin structures are nearly identical.
The copper(II) thiolate center is difficult to model.
EPR Spectra Distinguish the Three Types of Copper Found in Metalloproteins
CuA Model Chemistry: Reversible 1-Electron Transfer
-2.5-2.0-1.5-1.0-0.500.00.501.01.5
-0.6-0.4-0.200.20.40.6 ( ) . E V vs Cp2Fe+/Cp2Fe
Cu Cu
N
N
N N
N N
N N
SCu Cu
SN
N
His
NN
HisCys
Cys
O
S
Me
O
O OCu
O
CuO O
O O
N N
NN
Cu Cu
O O
R
3+
Met
Glu
CuA
+
+
= R Ph3 -C
-Cu Cu ( )dist Å
2.5-2.7
2.448
2.4246(12)
2.4500(15)
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.
LeCloux
Chuan He
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
Note again, minimal reorganization energy upon electron transfer
For [Fe(N4-porphyrin)(N-His)(S-Met)]
- e-
low spin ferrous low spin ferric
N
N
N
N
COO-
COO-
Fe
protoporphyrin IX
Long-Distance Electron Transfer in Proteins
O1 O2 O3
etc
R1 R2 R3
O = oxidized formR = reduced form
Three ways to measure:
1. Self-exchange
2. Artificial donor-acceptor pairs3. Study of natural protein redox pairs
RedAz+ OxAz OxAz + RedAz
CuI CuII CuII CuI
k = 1.3 x 106 M-1 s-1 for azurin
Artificial Donor-Acceptor Pairs
Cytochrome c; Fe---Ru, ~12 Å