Sortaza
| Porodica sortaza | |
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| Identifikatori | |
| Simbol | 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.[2][3] 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.[4][5][6]
Reakcija[uredi | uredi izvor]
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.[7][8]
Biološka uloga[uredi | uredi izvor]
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.[9]
Kao cilj antibiotika[uredi | uredi izvor]
Smatra se da su sortaze dobre mete za nove antibiotike [10] budući da su važni proteini za patogene bakterije i barem jedna kompanija zabilježila je ograničeni komercijalni interes.[11]
Struktura[uredi | uredi izvor]
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.[12]
Upotreba u strukturnoj biologiji[uredi | uredi izvor]
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 [13] and in one example by X-ray crystallographers to promote complex formation.[14]
Također pogledajte[uredi | uredi izvor]
Reference[uredi | uredi izvor]
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- ^ LeMieux J, Woody S, Camilli A (September 2008). "Roles of the sortases of Streptococcus pneumoniae in assembly of the RlrA pilus". Journal of Bacteriology. 190 (17): 6002–13. doi:10.1128/JB.00379-08. PMC 2519520. PMID 18606733.
- ^ Kang HJ, Coulibaly F, Proft T, Baker EN (January 2011). Hofmann A (ured.). "Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly". PLOS ONE. 6 (1): e15969. Bibcode:2011PLoSO...615969K. doi:10.1371/journal.pone.0015969. PMC 3019223. PMID 21264317.
- ^ Mazmanian SK, Liu G, Ton-That H, Schneewind O (July 1999). "Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall". Science. 285 (5428): 760–3. doi:10.1126/science.285.5428.760. PMID 10427003.
- ^ Cossart P, Jonquières R (May 2000). "Sortase, a universal target for therapeutic agents against gram-positive bacteria?". Proceedings of the National Academy of Sciences of the United States of America. 97 (10): 5013–5. Bibcode:2000PNAS...97.5013C. doi:10.1073/pnas.97.10.5013. PMC 33977. PMID 10805759.
- ^ Haft DH, Payne SH, Selengut JD (January 2012). "Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification". Journal of Bacteriology. 194 (1): 36–48. doi:10.1128/JB.06026-11. PMC 3256604. PMID 22037399.
- ^ Maresso AW, Schneewind O (March 2008). "Sortase as a target of anti-infective therapy". Pharmacological Reviews. 60 (1): 128–41. doi:10.1124/pr.107.07110. PMID 18321961. S2CID 358030.
- ^ SIGA Technologies (September 2006). "Schedule 14A". U.S. Securities and Exchange Commission. Pristupljeno 29 October 2009.
- ^ Pallen MJ, Lam AC, Antonio M, Dunbar K (March 2001). "An embarrassment of sortases - a richness of substrates?". Trends in Microbiology. 9 (3): 97–102. doi:10.1016/S0966-842X(01)01956-4. PMID 11239768.
- ^ Kobashigawa Y, Kumeta H, Ogura K, Inagaki F (March 2009). "Attachment of an NMR-invisible solubility enhancement tag using a sortase-mediated protein ligation method". Journal of Biomolecular NMR. 43 (3): 145–50. doi:10.1007/s10858-008-9296-5. PMID 19140010. S2CID 207183676.
- ^ Wang Y, Pascoe HG, Brautigam CA, He H, Zhang X (October 2013). "Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin". eLife. 2: e01279. doi:10.7554/eLife.01279. PMC 3787391. PMID 24137545.
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