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SERINE/THREONINE PROTEIN KINASE

Gene Name - StkP

Cell Location - StkP is located in the cell membrane and is a single-pass transmembrane serine/threonine kinase protein [1][2]. 

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FUNCTION                                                                                                                                                                             

  • StkP plays a role in the signalling and regulating of gene expression, with its importance in this process being widely recognised.

  • It plays major roles in cell wall synthesis and cell division [1] [3].

  • StkP helps to control the formation of new cell walls between two daughter cells during cell division by signalling cell wall status information to other key proteins involved in cell division.  

  • It also functions as an aid in other complex processes within the cell such as cellular metabolism, fitness, and aiding in in the introduction of foreign DNA into the cell by signalling transduction pathways.

STRUCTURE                                                                                                                                                                           

litemol_screenshot STKP.png

Click on the image for more information on the secondary and tertiary structure of Serine/Threonine Protein Kinase.

PROTEIN SEQUENCE                                                                                                                                                       

10                         20                         30                         40                         50
MIQIGKIFAG      RYRIVKQIGR       GGMADVYLAK   DLILDGEEVA       VKVLRTNYQT
60                         70                         80                         90                         100
DPIAVARFQR     EARAMADLDH    PHIVRITDIG        EEDGQQYLAM  EYVAGLDLKR
110                       120                       130                       140                       150
YIKEHYPLSN       EEAVRIMGQI      LLAMRLAHTR     GIVHRDLKPQ     NILLTPDGTA
160                       170                       180                       190                       200
KVTDFGIAVA      FAETSLTQTN      SMLGSVHYLS     PEQARGSKAT    VQSDIYAMGI
210                       220                       230                       240                       250
IFYEMLTGHI        PYDGDSAVTI     ALQHFQKPLP     SVIAENPSVP      QALENVIIKA
260                       270                       280                       290                       300
TAKKLTNRYR      SVSEMYVDLS      SSLSYNRRNE     SKLIFDETSK        ADTKTLPKVS
310                       320                       330                       340                       350
QSTLTSIPKV        QAQTEHKSIK    NPSQAVTEET     YQPQAPKKHR    FKMRYLILLA
360                       370                       380                       390                       400
SLVLVAASLI         WILSRTPATI        AIPDVAGQTV     AEAKATLKKA     NFEIGEEKTE
410                       420                       430                       440                       450      

ASEKVEEGRI      IRTDPGAGTG     RKEGTKINLV       VSSGKQSFQI     SNYVGRKSSD
460                       470                       480                       490                       500
VIAELKEKKV       PDNLIKIEEE        ESNESEAGTV     LKQSLPEGTT     YDLSKATQIV
510                       520                       530                       540                       550
LTVAKKATTI        QLGNYIGRNS    TEVISELKQK       KVPENLIKIE         EEESSESEPG
560                       570                       580                       590                       600     

TIMKQSPGAG    TTYDVSKPTQ     IVLTVAKKVT        SVAMPSYIGS      SLEFTKNNLI
610                       620                       630                       640                       650
QIVGIKEANI       EVVEVTTAPA      GSAEGMVVEQ   SPRAGEKVDL     NKTRVKISIY
KPKTTSATP  

SEQUENCE LENGTH - 659

CURRENT FIELD STATUS

cdc-IFpQtennlj8-unsplash.jpg

CURRENT TRIAL STATUS

Phase 1

  • Immunisation of mice with StkP 

  • Immunisation of combination vaccine containing StkP, PsaA, and PcsB 

michael-longmire-L9EV3OogLh0-unsplash.jp

IMMUNE RESPONSE GENERATED

  • In vitro studies show StkP is accessible on the pneumococcal cell surface to antibodies in humans and mice.

  • StkP is shown to protect against lethal forms of sepsis and pneumonia.

  • Sktp has been shown to be safe to use, well tolerated within the body, and highly immunogenic in clinical trials when used in a SktP-PsaA-PcsB combination vaccine in adults. This was measured using Immunoglobulin G responses specific to each protein. 

cdc-ljiPMfg-0m0-unsplash.jpg

MECHANISM OF VIRULENCE

• Surface-exposed protein, therefore, increases virulence as it plays a key role in the infectious process of Streptococcus pneumoniae.
• StkP is a non-classical protein that has strong links to the pathogenicity of Streptococcus pneumoniae as can influence the colonisation and spreading of bacteria.
• StkP has been proven to increase virulence in mouse models infected with S. pneumoniae.

RELATED GENE BANKS                                                                                                                                                    

RELATED ARTICLES                                                                                                                                                            

[1]        L. Nováková et al., “Identification of multiple substrates of the StkP Ser/Thr protein kinase in Streptococcus pneumoniae,” Journal of Bacteriology, vol. 192, no. 14, pp. 3629–3638, Jul. 2010, doi: 10.1128/JB.01564-09.

 

[2]        J. Echenique, A. Kadioglu, S. Romao, P. W. Andrew, and M. C. Trombe, “Protein Serine/Threonine Kinase StkP Positively Controls Virulence and Competence in Streptococcus pneumoniae,” Infection and Immunity, vol. 72, no. 4, pp. 2434–2437, Apr. 2004, doi: 10.1128/IAI.72.4.2434-2437.2004.

 

[3]        K. Beilharz, L. Nováková, D. Fadda, P. Branny, O. Massidda, and J. W. Veening, “Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 15, pp. E905–E913, Apr. 2012, doi: 10.1073/pnas.1119172109.

 

[4]        C. Giefing, K. E. Jelencsics, D. Gelbmann, B. M. Senn, and E. Nagy, “The pneumococcal eukaryotic-type serine/threonine protein kinase StkP co-localizes with the cell division apparatus and interacts with FtsZ in vitro,” Microbiology, vol. 156, no. 6, pp. 1697–1707, Jun. 2010, doi: 10.1099/mic.0.036335-0.

 

[5]        R. Dias, D. Félix, M. Caniça, and M. C. Trombe, “The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins,” BMC Microbiology, vol. 9, 2009, doi: 10.1186/1471-2180-9-121.

 

[6]        K. Moffitt and R. Malley, “Rationale and prospects for novel pneumococcal vaccines,” Human Vaccines and Immunotherapeutics, vol. 12, no. 2, pp. 383–392, Feb. 2016, doi: 10.1080/21645515.2015.1087625.

 

[7]        T. Lagousi, P. Basdeki, J. Routsias, and V. Spoulou, “Novel protein-based pneumococcal vaccines: Assessing the use of distinct protein fragments instead of full-length proteins as vaccine antigens,” Vaccines, vol. 7, no. 1. MDPI AG, 2019, doi: 10.3390/vaccines7010009.

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