Frontiers in Protein and Peptide Sciences

Volume: 1

Analysis of Sequence Divergence in Metabolic Proteins of Plasmodium falciparum: Implications for Remote Homology Detection

Author(s): Smita Mohanty, Gayatri Ramakrishnan, Pratik Dave and Narayanaswamy Srinivasan

Pp: 226-272 (47)

DOI: 10.2174/9781608058624114010014

* (Excluding Mailing and Handling)

Abstract

Plasmodium falciparum, an obligate intracellular parasite and causative agent of malaria, exhibits an atypical metabolic organization of proteins which are diverged extensively from their homologues in other organisms. This divergence makes homology-based on structural and functional annotation of the proteins difficult. With an emphasis on determinant aspects such as domain duplication, divergence and domain splitting, we provide a comprehensive basis to understand the significance of sequence divergence observed in metabolic proteins of P. falciparum. Such a pronounced sequence divergence in proteins renders the homology-based annotation transfer nontrivial. Additionally the unavailability of function annotation for about 40% of the parasitic proteome poses a limitation to understand the physiological basis of metabolic flexibility exhibited by the parasite to facilitate its multi-host survival. Thus, detection and exploration of remotely related homologues with the help of highly sensitive sequence search techniques become indispensable. Employment of a combination of highly sensitive profile-based approaches has enabled enhanced structural and functional characterization of metabolic proteins along with identification of proteins potentially involved in metabolic pathways. An enriched function annotation of the parasitic protein repertoire not only facilitates recognition of putative pathway proteins but also paves way for prioritizing targets for chemotherapeutic interventions.


Keywords: Metabolic enzymes, metabolic pathways, Plasmodium falciparum, protein evolution, remote homology detection.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6555) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6555) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740346521 and j.to_date >= 1740346521 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6555)
      640μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1519 and `b`.`banner_from_date` <= 1740346521 and `b`.`banner_to_date` >= 1740346521 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.17msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1519
      • 3: 1740346521
      • 4: 1740346521
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='f9916b6c27b8c895fa21e76b11c20a2c'
      420μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    5Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        eEymLYWtPG2ttl0N7bF4XhdqCQUhN7HVE5OEJAVO
        uc_cart_id
        f9916b6c27b8c895fa21e76b11c20a2c
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6555" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/6555
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImpWbCtPMEhaYXZUc2JPUTFkb3gwd3c9PSIsInZhbHVlIjoiKzFkN3BXNi9KZlBsYUJHTHgxRngzMWM0ZHZJYW5aZ0hIZldtcXpUWG50TT0iLCJtYWMiOiJjZDAzMWEyZTM2ZTQ0ZDg3YTJiNGZmOWM4MzIzZDVmOGUxZjRlOWQ3ZTc4MmRiYmEzOTFjZjgyZjQ2NjkyNzBiIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImpWbCtPMEhaYXZUc2JPUTFkb3gwd3c9PSIsInZhbHVlIjoiKzFkN3BXNi9KZlBsYUJHTHgxRngzMWM0ZHZJYW5aZ0hIZldtcXpUWG50TT0iLCJtYWMiOiJjZDAzMWEyZTM2ZTQ0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Sun, 23 Feb 2025 21:35:21 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlBZW5IcEVNTDc0d2lMSFYrMDVvQUE9PSIsInZhbHVlIjoiSUpOQWxua242V0R0TDB4RHBSY3F5ZVU1UVBSQ2NvZitXSFNldmVzcVpjR1E1WlFqMm5lTy81ZUYrcEdCdVVVRUVsSUNEU1c4RTlVZUsrd1NObENkcjRpL3BEbEtlTERtSnJmd2o0RnZyTDNUZVBhallJU1pqZm9Od1A3dG9hYkciLCJtYWMiOiJlMzcxZTllMDdhOWUzZjdlOWU1ZWMxMWQxMzE3M2YwMTk0MmJjZmNhYjYwNTIwNzhjNWZmMjdlNjhkMjgyY2U5IiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:35:21 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjlBZW5IcEVNTDc0d2lMSFYrMDVvQUE9PSIsInZhbHVlIjoiSUpOQWxua242V0R0TDB4RHBSY3F5ZVU1UVBSQ2NvZitXSFNldmVzcVpjR1E1WlFqMm5lTy81ZUYrcEdCdVVVRUVsSUNEU" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkJJUDFaT0VKdDhsWUY2YkRJNXJ1TVE9PSIsInZhbHVlIjoic2pPTmhJT1o1SjVIZ0ZFMEJMb1U5WmtvaFAzeHI4dmRNQjBaQUVOUVduQjRSKzhYekVnVlZSQWNkUTZqMCtQNUJYRUtQM0xVbGd3cU15cTNKc3ZVVC92MytGa0haQThpc01lNzV2ZklSc2daUmk2SFpRa25IMloySi82MVVUcHIiLCJtYWMiOiJjMGU5ZmUyYTc2NjQ2NmUzYjEyZmYyYmI1MzI5ZWQ3YzQ3MjFkODcyOTk0MjU3MmQwNDAwYzRiMGQ0MTFkNzY4IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkJJUDFaT0VKdDhsWUY2YkRJNXJ1TVE9PSIsInZhbHVlIjoic2pPTmhJT1o1SjVIZ0ZFMEJMb1U5WmtvaFAzeHI4dmRNQjBaQUVOUVduQjRSKzhYekVnVlZSQWN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlBZW5IcEVNTDc0d2lMSFYrMDVvQUE9PSIsInZhbHVlIjoiSUpOQWxua242V0R0TDB4RHBSY3F5ZVU1UVBSQ2NvZitXSFNldmVzcVpjR1E1WlFqMm5lTy81ZUYrcEdCdVVVRUVsSUNEU1c4RTlVZUsrd1NObENkcjRpL3BEbEtlTERtSnJmd2o0RnZyTDNUZVBhallJU1pqZm9Od1A3dG9hYkciLCJtYWMiOiJlMzcxZTllMDdhOWUzZjdlOWU1ZWMxMWQxMzE3M2YwMTk0MmJjZmNhYjYwNTIwNzhjNWZmMjdlNjhkMjgyY2U5IiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:35:21 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjlBZW5IcEVNTDc0d2lMSFYrMDVvQUE9PSIsInZhbHVlIjoiSUpOQWxua242V0R0TDB4RHBSY3F5ZVU1UVBSQ2NvZitXSFNldmVzcVpjR1E1WlFqMm5lTy81ZUYrcEdCdVVVRUVsSUNEU" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkJJUDFaT0VKdDhsWUY2YkRJNXJ1TVE9PSIsInZhbHVlIjoic2pPTmhJT1o1SjVIZ0ZFMEJMb1U5WmtvaFAzeHI4dmRNQjBaQUVOUVduQjRSKzhYekVnVlZSQWNkUTZqMCtQNUJYRUtQM0xVbGd3cU15cTNKc3ZVVC92MytGa0haQThpc01lNzV2ZklSc2daUmk2SFpRa25IMloySi82MVVUcHIiLCJtYWMiOiJjMGU5ZmUyYTc2NjQ2NmUzYjEyZmYyYmI1MzI5ZWQ3YzQ3MjFkODcyOTk0MjU3MmQwNDAwYzRiMGQ0MTFkNzY4IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkJJUDFaT0VKdDhsWUY2YkRJNXJ1TVE9PSIsInZhbHVlIjoic2pPTmhJT1o1SjVIZ0ZFMEJMb1U5WmtvaFAzeHI4dmRNQjBaQUVOUVduQjRSKzhYekVnVlZSQWN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "eEymLYWtPG2ttl0N7bF4XhdqCQUhN7HVE5OEJAVO" "uc_cart_id" => "f9916b6c27b8c895fa21e76b11c20a2c" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6555" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:35:21GET/chapter/6555112197