Principles of Bioinorganic Chemistry - 2004.
The grade for this course will be determined by a term exam (35%), a written research paper with oral presentation (55%), and problem sets (10%). The oral presentations will be held in research conference style at an all-day symposium at MIT on Saturday, October 30th. Please reserve the date for there are no excused absences. Papers are due October 28th. Problem sets are due one week after their assigned date. Recitations are held at 5 PM on Mondays.
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Baker, Anderson, and Baker, PNAS, 2003, 100, 3579.
Nomenclature: Fbp, ferric binding proteins
n, for Neisseria meningitidis
Iron must bind as Fe(III), or the ferric state. If reduced, a bacterial reductase must be involved, thus affording control of iron binding and uptake in the organism (see E1/2 values in the table above.
Crumbliss, et al. PNAS, 2003, 100, 3659.
in Cells by Receptor-Mediated Endocytosis
Central dogma of molecular biology:
DNA mRNA Protein
Mixed-valent polyiron oxo cluster prepared as a model for ferritin core formation intermediates.
Taft, et al., Science1993, 259, 1302
Overall formula: [Fe12O2 (OCH3)18(O2CCH3) 6(CH3OH)n]
Only Iron-Loaded Transferrin Binds to the Receptor
A single protein, Fur (for iron uptake regulator), controls the transcription of genes involved in siderophore biosynthesis. Fur is a dimer with subunits of Mr 17 kDa. At high iron levels, the Fur protein has bound metal and interacts specifically with DNA repressing transcription.
Expression of ferritin and the transferrin receptor is regulated at the translational level.
Iron-responsive protein (IRP)
Stem-loop structure in the mRNA
High Fe, low TfR, high Ft
Low Fe, high TfR, low Ft
Contains an Fe4S4 Cluster
Cluster assembled in
protein, which then dissociates from
Apoprotein stays associated with
Mercury in the environment of industrial plants is converted by bacterial to harmful organomercury compounds. Fish and other plant and animal life assimilate the mercury which ultimately enters the
human food chain. Bacteria defend themselves against
the mercury by using the proteins listed below.
Mercuric ion reductase
MerR, the intracellular mercuric ion sensor
Transcription of the genes encoding the proteins is
controlled by MerR in response to mercury levels
Reductase: no structural or detailed mechanistic information
EXAFS spectroscopy and chemical modification experiments indicate that Hg-MerR has a 3-coordinate, Hg(S-Cys)3
environment with an average Hg–S distance of 2.43 Å.
This unusual tridentate heavy metal receptor site is consistent
with the thermodynamic stability of [Hg(SR) 3]- complexes and may account both for the high affinity of the Hg(II) binding and for
the selectivity for Hg(II) over other soft metal ions that
prefer tetrahedral metal-thiolate coordination.