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Microcrystal in human urine
NH4MgPO4·6H2O
Calcium phosphate
Hydroxylapatite
Ca10(PO4)6(OH)2
Calcium oxalate
Calcium oxalate
Calcium oxalate in garlic skin, Rogelio Moreno, Polarized light microscopy
“Models for protein binding to calcium oxalate surfaces”,
A. Gul and P. Rez, Urol. Res. 35, (2007), 63-71
Many think that Negatively charged amino acids
(deprotonated aspartic and glutamatic acid) bind
Calcium.
Calcium oxalate stone matrix proteins:
Prothrombin fragment 1, bikunin,
β-microglobulin, transferrin, antitrypsin
How these proteins bind to crystal surface?
They inhibit the growth or act as nucleation sites?
Kidney stones
Calcium oxalate crystals
form for alkaline urine pH>5.5
Kidney stones Calcium oxalate crystal form for Urine pH>5.5
2009, Lawrence Livermore National Laboratory
Aspartic acid-rich peptides adsorbed on a calcium oxalate monohydrate (COM) crystal
surface. AFM image collected during growth of the [010] face of COM
1296->139 conformers
Six most stable aspartic acid
conformers in gas
M.E.Sanz e al., Phys. Chem. Chem.
Phys., 2010,12, 3573
More energy
to produce,
but less toxic
Guano
Urea crystal cif file GaussView
Space group P421m, No. 113 (tetragonal)
Lattice parameters a=5.661A, b=5.661A, c=4.712A
http://rruff.geo.arizona.edu/AMS/CIF_text_files/10256_cif.txt
Blood serum
High level of uric acid  gout
Low level of uric acid  multiple
sclerosis
DNA base
purine
xanthine oxidase
Human, some primates, dalmatians without urate oxidase
Humans do have a gene for urate oxidase, but it is nonfunctional
Urate oxidase enzime
Relatively insoluble
Relatively soluble
The gene for urate oxidase was mutated during the evolution of humans to
provide us with a benefit for aging. Uric acid is a powerful antioxidant, and the
higher levels in our blood, caused by the evolutionary loss of urate oxidase,
may help protect us from oxygen damage over our long lifespans.
20-25 millions years ago
Cysteine
Cystine
(hexagonal P6122 space group,
a = b = 0.5422 nm, c =5.6275 nm)
Crystallization of L-cystine is a
critical step in the pathogenesis of
cystine kidney stones.
Crystal Growth Inhibitors for the Prevention of LCystine Kidney Stones Through Molecular Design
Jeffrey D. Rimer, Zhihua An, Zina Zhu, Michael H. Lee,
David S. Goldfarb, Jeffrey A. Wesson, Michael D. Ward
L-Cystine crystals grown
with CDME (bottom) are an
order of magnitude smaller
than those grown without the
molecular mimic (top) .
Science 330(2010)337
Cystinosis
Cystinosis
Cystine-depleting medications are available to
treat nephropathic cystinosis.
In a treated cystinotic lysosome, cystinedepleting medications modify cystine to
resemble lysine, thus enabling it to go through
the lysine transporter. It slows accumulation and
crystallization. This may help delay disease
progression.
Cystine-depleting medications do not appear to
remove previously accumulated crystals in the
body or reverse previous damage to the cells.
Cysteamine
Cysteamine bitartrate
(1976)
lysine