Staphylococcus aureus sortase A contributes to the Trojan horse mechanism of immune defense evasion with its intrinsic resistance to Cys184 oxidation.
Staphylococcus aureus sortase A contributes to the Trojan horse mechanism of immune defense evasion with its intrinsic resistance to Cys184 oxidation.
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金黄色葡萄球菌分选酶 A 凭借其对 Cys184 氧化的内在抵抗力，有助于免疫防御逃避的特洛伊木马机制。
DOI：
10.1021/bi200844h
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
McCafferty,DeweyG
中科院分区：
文献类型：
--
作者：
Melvin,JeffreyA;Murphy,ChristineF;Dubois,LauraG;Thompson,JWill;Moseley,MArthur;McCafferty,DeweyG
Staphylococcus aureusis a Gram-positive bacterial pathogen that causes serious infections which have become increasingly difficult to treat due to antimicrobial resistance and natural virulence strategies. Bacterial sortase enzymes are important virulence factors and good targets for future antibiotic development. It has recently been shown that sortase enzymes are integral to bacterial survival of phagocytosis, an underappreciated, but vital, step inS. aureuspathogenesis. Of note, the reaction mechanism of sortases relies on a solvent-accessible cysteine for transpeptidation. Because of the common strategy of oxidative damage employed by professional phagocytes to kill pathogens, it is possible that this cysteine may be oxidized inside the phagosome, thereby inhibiting the enzyme. This study addresses this apparent paradox by assessing the ability of physiological reactive oxygen species, hydrogen peroxide and hypochlorite, to inhibit sortase A (SrtA) fromS. aureus. Surprisingly, we found that SrtA is highly resistant to oxidative inhibition, bothin vitroandin vivo. The mechanism of resistance to oxidative damage is likely mediated by maintaining a high reduction potential of the catalytic cysteine residue, Cys184. This is due to the unusual active site utilized byS. aureusSrtA, which employs a reverse protonation mechanism for transpeptidation, resulting in a high pKaas well as reduction potential for Cys184. The results of this study suggest thatS. aureusSrtA is able to withstand the extreme conditions encountered in the phagosome and maintain function, contributing to survival of phagocytotic killing.
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辣根亚铁过氧化物酶与过氧化氢的反应。
DOI：
10.1016/s0021-9258(18)63167-9
发表时间：
1970
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Noble;Q. H. Gibson
通讯作者：
Q. H. Gibson
DOI：
10.1016/s0924-8579(09)70004-4
发表时间：
2008-12-01
影响因子：
10.8
作者：
Song, Jae-Hoon
通讯作者：
Song, Jae-Hoon
影响因子：
4.8
作者：
Bentley, Matthew L.;Gaweska, Helena;McCafferty, Dewey G.
通讯作者：
McCafferty, Dewey G.
影响因子：
2.9
作者：
Lohse, DL;Denu, JM;Dixon, JE
通讯作者：
Dixon, JE
影响因子：
15
作者：
Frankel, BA;Bentley, M;McCafferty, DG
通讯作者：
McCafferty, DG