![Page 1: c o n d e n s a z io n e R - X H + H O - A R - X - A + H O ......Fig. 29.26c Cleavage of the C—N bond Glu-270 His-196 Arg-145 C02- HO Tyr-248 NH His-69 Glu-72 Arg-127 (c) Schematic](https://reader036.vdocument.in/reader036/viewer/2022071511/6130fa691ecc515869447116/html5/thumbnails/1.jpg)
R-XH + HO-A R-X-A + H2O
X = NH, A = -CO-R peptidasi, lactamasi, collagenasi
X = O, A = -CO-R esterasi
X = O, A = PO32-
fosfatasi, nucleasi
condensazione
idrolisi
Zn2+ -
Substrato+
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Anidrasi carbonica
30 kDa, 259 a.a.
k ≈ 10–1 s–1 → 106 s–1
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Sito catalitico della anidrasi carbonica
C OO
- 2+ -
acido di Lewis
base di Lewis
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Ciclo catalitico della anidrasi carbonica
Rate limiting
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Regione idrofilica
Regione idrofobica
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34 kDa, 300 a.a.
Carbossipeptidasi A (CPD A)
idrolisi di amminoacidi C-terminali
k ≈ 10–11 s–1 → 104 s–1
![Page 7: c o n d e n s a z io n e R - X H + H O - A R - X - A + H O ......Fig. 29.26c Cleavage of the C—N bond Glu-270 His-196 Arg-145 C02- HO Tyr-248 NH His-69 Glu-72 Arg-127 (c) Schematic](https://reader036.vdocument.in/reader036/viewer/2022071511/6130fa691ecc515869447116/html5/thumbnails/7.jpg)
Siti attivi di carbossipeptidasi
Carbossipeptidasi A (CPD A, bovino) Carbossipeptidasi G2 (CPG2, batterio)
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Posizionamento del substrato vicino al sito attivo della CPA
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Attivazione dell’acqua e suo attacco nucleofilo
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Rottura del legame peptidico C-N
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Trasferimento di un protone con formazione di NH3+ e del carbossilato
![Page 12: c o n d e n s a z io n e R - X H + H O - A R - X - A + H O ......Fig. 29.26c Cleavage of the C—N bond Glu-270 His-196 Arg-145 C02- HO Tyr-248 NH His-69 Glu-72 Arg-127 (c) Schematic](https://reader036.vdocument.in/reader036/viewer/2022071511/6130fa691ecc515869447116/html5/thumbnails/12.jpg)
Matrix Metalloproteinases (MMPs) +
Tissue Inhibitors of MetalloProteinases (TIMPs)
= Zn
= Ca
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Processo metastatico favorito da MMP
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Cromatina e Nucleosomi
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Sito attivo di HDAC8
Lisina acetilata
Aspartati
![Page 17: c o n d e n s a z io n e R - X H + H O - A R - X - A + H O ......Fig. 29.26c Cleavage of the C—N bond Glu-270 His-196 Arg-145 C02- HO Tyr-248 NH His-69 Glu-72 Arg-127 (c) Schematic](https://reader036.vdocument.in/reader036/viewer/2022071511/6130fa691ecc515869447116/html5/thumbnails/17.jpg)
HDAC Inhibitors (HDACi)
agenti antitumorali (modulazione epigenetica del DNA)
Zolinza®
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Zinc fingers
gene regulatory proteins e transcription factors
a-elica b-sheet
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a-elica
b-sheet
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Interazione di zinc-fingers con DNA