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</div> </div> <div id="email-action-panel" class="email-action-panel action-panel" aria-hidden="true" data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback" data-recaptcha-enabled="true"> <div class="inner-wrap"> <h2 class="action-panel-heading">Email citation</h2> <form id="email-action-panel-form" class="action-panel-content action-form" action="/send-email/" data-by-search-action="/results-export-email-by-search-data/" data-by-ids-action="/send-email/" data-by-search-method="post" data-by-ids-method="post" method="post"><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <div class="action-panel-control-wrap"><span class="action-panel-label"> Subject: </span> <span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 17504214 - PubMed</span> <input type="hidden" name="email-subject" value="1 selected item: 17504214"> <input type="hidden" name="email-subject-hash" value="daad4b9582d3fb4fbfe3b7a8ae8bef5e4b1ee440905f93563f268445f1bac78f"> </div> <div class="action-panel-control-wrap"><label for="email-to" class="action-panel-label required-field-asterisk"> To: </label> <input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required> </div> <div class="action-panel-control-wrap"><label for="email-from" class="action-panel-label"> From: </label> <input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256"> </div> <div class="action-panel-control-wrap"><label for="email-citation-format" class="action-panel-label"> Format: </label> <select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format"> <option selected value="summary">Summary</option> <option value="summary-text">Summary (text)</option> <option value="abstract">Abstract</option> <option value="abstract-text">Abstract (text)</option> </select> </div> <div class="include-supplemental-container"><input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental"> <label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label> </div> <div class="form-field recaptcha "> <div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div> </div> <div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="email" data-ga-label="send"> Send email </button> <button class="action-panel-cancel" aria-label="Close 'Email citations' panel" ref="linksrc=close_email_panel" aria-controls="email-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="email" data-ga-label="cancel"> Cancel </button> </div><input type="hidden" name="email-search-details" value=""> <input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524"> </form> </div> </div> <div id="collections-action-panel" class="collections-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-collections-open-panel-enabled="false" data-collections-open-panel-url-hash="#open-collections-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading">Add to Collections</h3> <form id="collections-action-panel-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <div class="choice-group" role="radiogroup"> <ul class="radio-group-items"> <li><input type="radio" id="collections-action-panel-new" class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label></li> <li><input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label></li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/17504214/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading">Add to My Bibliography</h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li><input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked> <label for="my-bibliography">My Bibliography</label></li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br><a href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/17504214/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto#">Please try again</a> </div> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading">Your saved search</h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <div class="action-panel-control-wrap"><label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"><label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"><a href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/17504214/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"><span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"><legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li><input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label></li> <li><input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label></li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"><label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"><label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"><label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"><label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"><label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"><label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div><input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"><label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading">Create a file for external citation management software</h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <input name="results-format" type="hidden" value="pubmed"> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading">Your RSS Feed</h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""><input type="hidden" name="csrfmiddlewaretoken" value="VtuN5Os6qmQS5kPr7SBYCi71Ll0w1QhACkLvhhgy19fNlhAJHdKK5cutwAKByYHD"> <div class="action-panel-control-wrap"><label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"><label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected>15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"><label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="17504214"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title">Full text links</h3> <div class="full-text-links-list"><a class="link-item dialog-focus" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://www.eurekaselect.com/59117/article" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3037&itool=Abstract-def&log$=linkouticon&uid=17504214&db=pubmed&nlmid=9440157" title="See full text options at Bentham Science Publishers Ltd." data-ga-category="full_text" data-ga-action="Bentham Science Publishers Ltd." data-ga-label="17504214"><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.eurekaselect.com-sites-all-themes-eurekaselect-images-ben_pubmed_flag1.gif" alt="full text provider logo"><span class="text"> Bentham Science Publishers Ltd. </span></a> </div> </div> <div class="short-view"><a 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id="full-view-heading"> <div class="article-citation"> <div class="publication-type"> Review </div> <div class="article-source"> <div class="journal-actions dropdown-block"> <button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Current medicinal chemistry" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Current medicinal chemistry" data-pinger-ignore> Curr Med Chem </button> <div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Current medicinal chemistry"> <div class="title"> Actions </div> <div class="content"> <ul class="journal-actions-links"> <li><a class="search-in-pubmed-link dropdown-block-link" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=%22Curr+Med+Chem%22%5Bjour%5D&sort=date&sort_order=desc&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" 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href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/17504214/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Bertoldi+M&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mariarita Bertoldi">Mariarita Bertoldi</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Contestabile+R&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Roberto Contestabile">Roberto Contestabile</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" 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ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Roberto Contestabile">Roberto Contestabile</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Bettati+S&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stefano Bettati">Stefano Bettati</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Cellini+B&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Barbara Cellini">Barbara Cellini</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=di+Salvo+ML&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Martino Luigi di Salvo">Martino Luigi di Salvo</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Borri-Voltattorni+C&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carla Borri-Voltattorni">Carla Borri-Voltattorni</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Bossa+F&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Francesco Bossa">Francesco Bossa</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/?term=Mozzarelli+A&cauthor_id=17504214&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Andrea Mozzarelli">Andrea Mozzarelli</a></span> </div> </div> <div class="affiliations"> <h3 class="title">Affiliation</h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1"><sup class="key">1</sup> Dipartimento di Biochimica e Biologia Molecolare, Università di Parma, Italy.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li><span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">17504214</strong> </span></li> <li><span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.2174/092986707780597899&id_type=DOI" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://doi.org/10.2174/092986707780597899" data-ga-category="full_text" data-ga-action="DOI"> 10.2174/092986707780597899 </a> </span></li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"> <div class="inner-wrap"> <button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/17504214/citations/" data-citation-style="nlm" data-pubmed-format-link="/17504214/export/"><span 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id="abstract"> <h2 class="title">Abstract</h2> <div class="abstract-content selected" id="eng-abstract"> <p>The vitamin B(6)-derived pyridoxal 5'-phosphate (PLP) is the cofactor of enzymes catalyzing a large variety of chemical reactions mainly involved in amino acid metabolism. These enzymes have been divided in five families and fold types on the basis of evolutionary relationships and protein structural organization. Almost 1.5% of all genes in prokaryotes code for PLP-dependent enzymes, whereas the percentage is substantially lower in eukaryotes. Although about 4% of enzyme-catalyzed reactions catalogued by the Enzyme Commission are PLP-dependent, only a few enzymes are targets of approved drugs and about twenty are recognised as potential targets for drugs or herbicides. PLP-dependent enzymes for which there are already commercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially, tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological states associated to the GABA/glutamate equilibrium concentrations). Within each family or metabolic pathway, the enzymes for which drugs have been already approved for clinical use are discussed first, reporting the enzyme structure, the catalytic mechanism, the mechanism of enzyme inactivation or modulation by substrate-like or transition state-like drugs, and on-going research for increasing specificity and decreasing side-effects. Then, PLP-dependent enzymes that have been recently characterized and proposed as drug targets are reported. Finally, the relevance of recent genomic analysis of PLP-dependent enzymes for the selection of drug targets is discussed.</p> </div> </div> <p class="disclaimer" id="disclaimer"><a href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/disclaimer/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a></p> <div class="similar-articles" id="similar"> <h2 class="title">Similar articles</h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"><a class="docsum-title" href="https://pubmed-ncbi-nlm-nih-gov.translate.goog/30297752/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=auto" ref="article_id=30297752&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="30297752" data-ga-label=""> Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics. </a> <div class="docsum-citation full-citation"><span class="docsum-authors full-authors">Hoegl A, Nodwell MB, Kirsch VC, Bach NC, Pfanzelt M, Stahl M, Schneider S, Sieber SA.</span> <span class="docsum-authors short-authors">Hoegl A, et al.</span> <span class="docsum-journal-citation full-journal-citation">Nat Chem. 2018 Dec;10(12):1234-1245. doi: 10.1038/s41557-018-0144-2. 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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=17504214&ordinalpos=1&linkpos=2"> Gene </a></li> <li><a title="Related information in MedGen" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://www.ncbi.nlm.nih.gov/medgen?linkname%3Dpubmed_medgen%26from_uid%3D17504214" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=17504214&ordinalpos=1&linkpos=3"> MedGen </a></li> <li><a title="Published protein sequences" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://www.ncbi.nlm.nih.gov/protein?linkname%3Dpubmed_protein%26from_uid%3D17504214" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=17504214&ordinalpos=1&linkpos=4"> Protein </a></li> <li><a title="Link to Protein RefSeqs" href="https://translate.google.com/website?sl=auto&tl=en&hl=auto&u=https://www.ncbi.nlm.nih.gov/protein?linkname%3Dpubmed_protein_refseq%26from_uid%3D17504214" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=17504214&ordinalpos=1&linkpos=5"> Protein (RefSeq) </a></li> 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