Sortaza

Sortaza se odnosi na skupinu prokariotskih enzima koji modificiraju površinske proteine, prepoznavanjem i cijepanjem karboksilnog terminala sortirajući signal. Za većinu supstrata enzima sortaze, signal prepoznavanja sastoji se od motiva LPXTG (Leu-Pro-bilo koji-Thr-Gly), zatim visoko hidrofobnog transmembranske sekvence, nakon čega slijedi skupina baznih ostataka kao što je argininski. Do cijepanja dolazi između Thr i Gly, s prolaznim vezanjem preko Thr ostatka na Cys ostatak aktivnog mjesta, nakon čega slijedi transpeptidacija koja kovalentno veže protein na komponente ćelijskog zida. Sortaze se javljaju u gotovo svim Gram-pozitivnim bakterijama i povremenim Gram-negativnim bakterijama (npr. Shewanella putrefaciens) ili Archaea (npr. Methanobacterium thermoautotrophicum), gdje dekoracija ćelijskog zida posredovana LPXTG-om nije prijavljena. Iako sortaza A, sortaza za "kućno održavanje", obično djeluje na mnoge proteinske mete, drugi oblici sortaze prepoznaju varijante oblika motiva cijepanja ili kataliziraju sklapanje pilina u pilusima.

Porodica sortaza
Sortaza C streptokoka grupe B povezana s pilusom. PDB pristup 3O0P
Identifikatori
Simbol	Sortaza

Reakcija

Sortaza Staphylococcus aureus je transpeptidaza koja veže površinske proteine na ćelijski zid; cijepa se između Gly i Thr motiva LPXTG i katalizira stvaranje amidne veze između karboksilne skupine treonina i amino skupine peptidoglikana ćelijskog zida.

Biološka uloga

Proteini supstrata vezani sortazama za ćelijske zidove uključuju enzime, piline i glikoproteine velike površine koji posreduju adheziju. Ovi proteini često imaju važnu ulogu u virulenciji, infekcijama i kolonizaciji patogena.

Površinski proteini ne samo da podstiču interakciju između invazivnog patogena i životinjskih tkiva, već također pružaju genijalne strategije za bijeg bakterija od imunskog odgovora domaćina. U slučaju S. aureus, protein A, imunoglobulini se hvataju na površini mikroba i kamufliraju bakterije tokom invazije tkiva domaćina. S. aureus mutanti kojima nedostaje gen srtA ne uspijevaju se usidriti i prikazati neke površinske proteine te im je smanjena sposobnost izazivanja infekcija kod životinja. Sortaza djeluje na površinske proteine koji se iniciraju u put sekrecije (Sec) i čiji signalni peptid uklanja signalna peptidaza. S. aureus genom kodira dva skupa gena sortaze i gena za lučenje. Zamislivo je da S. aureus razvio je više od jednog puta za transport 20 površinskih proteina do ovojnice ćelijskog zida.

Treba imati na umu da su egzosortaza i arheosortaza funkcionalno analogne, iako ni na koji način nisu homologne sortazi.

Kao cilj antibiotika

Smatra se da su sortaze dobre mete za nove antibiotike budući da su važni proteini za patogene bakterije i barem jedna kompanija zabilježila je ograničeni komercijalni interes.

Struktura

Ova skupina cistein-peptidaza pripada porodici MEROPS peptidaza C60 (klan C-) i uključuje članove nekoliko potporodica sortaza.

Druga potporodica sortaza (C60B u MEROPS) sadrži proteine bakterijske sortaze B koji su dugi po oko 200 ostataka.

Upotreba u strukturnoj biologiji

Transpeptidaznu aktivnost sortaze koriste strukturni biolozi za proizvodnju fuzijskih proteina in vitro. Motiv prepoznavanja (LPXTG) dodaje se na C-kraj proteina od interesa, dok se motiv oligo-glicina dodaje na N-terminal drugog proteina koji se vezuje. Nakon dodavanja sortaze u proteinsku smjesu, dva peptida su kovalentno vezana putem nativne peptidne veze. Ovu reakciju koriste NMR spektroskopisti za proizvodnju NMR nevidljivih oznaka topljivosti and in one example by X-ray crystallographers to promote complex formation.

Također pogledajte

• Proteinska oznaka
• Bioinženjerstvo
• HaloTag
• Inteini

Dopunska literatura

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Vanjski linkovi

Ovaj članak uključuje tekst iz javnog domena Pfam i InterPro: IPR005754