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        <title>Cryo-EM structure of the C. neoformans lipid flippase Apt1-Cdc50 bound with butyrolactol A in the E2P state</title>
        <authors_list>
            <author>Duan HD</author>
            <author>Li H</author>
        </authors_list>
        <keywords>Cryptococcus neoformans, lipid flippase, P4-ATPase, Cdc50 protein, butyrolactol A, TRANSLOCASE-INHIBITOR complex</keywords>
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        <citation_list>
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                    <author order="1">Chen X</author>
                    <author order="2">Duan HD</author>
                    <author order="3">Hoy MJ</author>
                    <author order="4">Koteva K</author>
                    <author order="5">Spitzer M</author>
                    <author order="6">Guitor AK</author>
                    <author order="7">Puumala E</author>
                    <author order="8">Fiebig AA</author>
                    <author order="9">Hu G</author>
                    <author order="10">Yiu B</author>
                    <author order="11">Chou S</author>
                    <author order="12">Bian Z</author>
                    <author order="13">Choi Y</author>
                    <author order="14">Guo ABY</author>
                    <author order="15">Wang W</author>
                    <author order="16">Sun S</author>
                    <author order="17">Robbins N</author>
                    <author order="18">Averette AF</author>
                    <author order="19">Cook MA</author>
                    <author order="20">Truant R</author>
                    <author order="21">MacNeil LT</author>
                    <author order="22">Brown ED</author>
                    <author order="23">Kronstad JW</author>
                    <author order="24">Coombes BK</author>
                    <author order="25">Cowen LE</author>
                    <author order="26">Heitman J</author>
                    <author order="27">Li H</author>
                    <author order="28">Wright GD</author>
                    <title>Butyrolactol A enhances caspofungin efficacy via flippase inhibition in drug-resistant fungi.</title>
                    <journal_abbreviation>Cell</journal_abbreviation>
                    <year>2025</year>
                    <external_references type="PUBMED">41478284</external_references>
                    <external_references type="DOI">doi:10.1016/j.cell.2025.11.036</external_references>
                    <external_references type="ISSN">1097-4172</external_references>
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                <journal_citation published="true">
                    <author order="29">Chen X</author>
                    <author order="30">Duan HD</author>
                    <author order="31">Hoy MJ</author>
                    <author order="32">Koteva K</author>
                    <author order="33">Spitzer M</author>
                    <author order="34">Guitor AK</author>
                    <author order="35">Puumala E</author>
                    <author order="36">Fiebig AA</author>
                    <author order="37">Hu G</author>
                    <author order="38">Yiu B</author>
                    <author order="39">Chou S</author>
                    <author order="40">Bian Z</author>
                    <author order="41">Choi Y</author>
                    <author order="42">Ya Guo AB</author>
                    <author order="43">Wang W</author>
                    <author order="44">Sun S</author>
                    <author order="45">Robbins N</author>
                    <author order="46">Averette AF</author>
                    <author order="47">Cook MA</author>
                    <author order="48">Truant R</author>
                    <author order="49">MacNeil LT</author>
                    <author order="50">Brown ED</author>
                    <author order="51">Kronstad JW</author>
                    <author order="52">Coombes BK</author>
                    <author order="53">Cowen LE</author>
                    <author order="54">Heitman J</author>
                    <author order="55">Li H</author>
                    <author order="56">Wright GD</author>
                    <title>Butyrolactol A potentiates caspofungin efficacy against resistant fungi via phospholipid flippase inhibition.</title>
                    <journal_abbreviation>Biorxiv</journal_abbreviation>
                    <country>US</country>
                    <year>2025</year>
                    <external_references type="PUBMED">39829750</external_references>
                    <external_references type="DOI">doi:10.1101/2025.01.06.630955</external_references>
                    <external_references type="ISSN">2692-8205</external_references>
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                <details>Cryo-EM structure of the C. neoformans lipid flippase Apt1-Cdc50 bound with butyrolactol A in the E2P state</details>
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    <sample>
        <name>Apt1-Cdc50 heterodimer bound with butyrolactol A</name>
        <supramolecule_list>
            <complex_supramolecule supramolecule_id="1">
                <name>Apt1-Cdc50 heterodimer bound with butyrolactol A</name>
                <parent>0</parent>
                <macromolecule_list>
                    <macromolecule>
                        <macromolecule_id>1</macromolecule_id>
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                    <macromolecule>
                        <macromolecule_id>2</macromolecule_id>
                    </macromolecule>
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                <natural_source database="NCBI">
                    <organism ncbi="235443">Cryptococcus neoformans var. grubii H99</organism>
                </natural_source>
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                    <theoretical units="MDa">0.222</theoretical>
                </molecular_weight>
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            <protein_or_peptide macromolecule_id="1">
                <name>Transcription regulator</name>
                <natural_source database="NCBI">
                    <organism ncbi="235443">Cryptococcus neoformans var. grubii H99</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.045937961</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="4932">Saccharomyces cerevisiae</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>MAIFNRKPKARLDGEPAPTEKEKVKWSKRPANTAFKQQRLKAWQPILTPKSVLPTLLIIGIIFAPIGALIVWGSGKVTTI
TLDYTECDVDAPTDGSYQAMPNSAYQYDLATSSSVSESSIASPTWTFSNDSSREVGETARCEIEFEVPYDLGPGLFLYYK
LTNYYQNHRRYSSSFDATQLIGDSRSLSQINGGNCKPITSRDGKPYYPCGLIANSLFNDTFPSVVLLNPTNGAQNQTYNF
SESGIAWGGIKKNYASTLTYISPSDVLPPPNWALKYPNGYVDGFPNLREDEHFQVWMRVAALPTFRKLWARNDGEIMSQG
RYRIVANMNYPVKQFSGTKSIVISTVSWIGGKQPFLGWAYIAAAILCVVLAVAGLIRHLVKPRKLGDMSLLSWNQPNANG
LHHHHHHHHHH</string>
                    <external_references type="UNIPROTKB">J9VW44</external_references>
                </sequence>
            </protein_or_peptide>
            <protein_or_peptide macromolecule_id="2">
                <name>Phospholipid-transporting ATPase</name>
                <natural_source database="NCBI">
                    <organism ncbi="235443">Cryptococcus neoformans var. grubii H99</organism>
                </natural_source>
                <molecular_weight>
                    <theoretical units="MDa">0.17653460899999998</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <recombinant_expression database="NCBI">
                    <recombinant_organism ncbi="4932">Saccharomyces cerevisiae</recombinant_organism>
                </recombinant_expression>
                <enantiomer>LEVO</enantiomer>
                <sequence>
                    <string>MGASKPPLVPRSKKHNPSWLDRNIVKPLESLAPSKLFARRRSPPVPRSVFINEPLPSEYYDKKGKILRAHHFATNQNVTS
KYTVITFIPKNLFEQFRRVANCFFLAISILQFFPKFSTISPGLVILPLIIVLAITALKDGYEDIKRHQADHRTNHAIVHV
LGGQDYTNQNPMASKDKTFIPAIPLPKRRSKKAKKAEEEAALNMQGRSSSTENFAAEPVPGAEPRGQDELQRMRSQVSNW
DEDPEAGDSPGELGWHRTIWEDVKVGDFVKIYENEQFPADIVICATSEEEDVAYIETKNLDGETNLKSRNGVPGLSHLNT
AEACAKAHLCIDLDAPESNMFRLNGAVINLEEYDEDEQHPIHPITLETTMLRGCVLKNTAWVIGIIVYTGEDTKIIRNAG
ATPSKRSKVEKQMNPQVIINLVILAAIAVVCAIVDHVNEVEWDRQQAYWMLFADTSGDNPNINGLVTFANAFITFQNIVP
ISLYISIEAVRTIQAAFIYWDRDIKYKKDGVTTRTTARSWNLSDDLGQIEYIFSDKTGTLTQNAMIFRQCSVGGKIYTGD
GLPPSHPTITHQHQPPPVHQHDDQDDPIAKSASESDDSDPKKISTEDPDEIKVTLPKEVLATFHDAELDKDLEAHDSEQS
RILHGFFAVLGLCHTVLAAETEPGVIEYKAQSPDEAALVQSAADVGFVFRGRDHNILRMSTPFSDVSDEYELLHVLEFNS
ARKRMSVILRKLDEDGRIFLLCKGADNVIFERLTKDSNQREMREKTDQDLQYFASEGLRTLCLAYRILDPQVYEQWAKEY
HNATVALQDREERIESVSSSIERDLILLGATAIEDKLQDGVPDTISDLKRAGIKVWVATGDKLETAVAIGYTTNLLTKDT
NLIVVREGRHSIGDQLREALEEFFGEDAGLRTTLSRIDSRRNSMDPPRLTRVNTGVRSLVGRDNGTRPGGFSLVIEGHAL
AHCFDDEETEALLLALSTRCNTVICCRVSPLQKAQIVHLIKDNLGVMCLAIGDGANDVSMIQAADVGVGISGEEGLQAVN
SSDYAIAQFRYLKRLLLVHGHWSYFRNSSMILNFFYKNIIGIGVLFWFMIYCGWSTTYVFAYVYLLFWNVFWTLVPVIAI
GLFDRNIDDETLMALPELYRASREGKYFGLMRFAYYIFEGVYQSAVIYFFLNYTYVTTTARGDGYDVYMYEMSTTQAIGA
VMVANLFSGLNIDAWTGWVWFAIWFGPFLIWVFTAVYSVIPPSSFYTGVYGNDVFLFRSAAYWFGWPFVTIIALLPRYLI
KTFRQNIFPNDVDTMRLVRKYHPEVDLYNHPMLGGKLAPKKDEDESDYGEEPFDGPEGRRSSIKMANLRHSHGAFGRGDQ
AGDMELGMGRKSLGNRPGLRSSMDSSRFGIHSGARGSTVDMSTGLEQPPSRGFGFTMEEGGVAIQRMQSRLSQTSSHASR
SRWPRFNNNSSSSHPFETKPPSSMSKLRSRAGSILTRKRADTTDTRNSDDKSLSSPVKTGFFGRHMPGQNHGQHEGRSMG
TPLKSETGRGDNWEEEELEDESLGRGFGVGQNMAPPEIPRMDYKDDDDKI</string>
                    <external_references type="UNIPROTKB">J9VZ19</external_references>
                </sequence>
                <ec_number>7.6.2.1</ec_number>
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            <ligand macromolecule_id="5">
                <name>2-acetamido-2-deoxy-beta-D-glucopyranose</name>
                <molecular_weight>
                    <theoretical units="MDa">0.000221208</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <formula>NAG</formula>
            </ligand>
            <ligand macromolecule_id="6">
                <name>BERYLLIUM TRIFLUORIDE ION</name>
                <molecular_weight>
                    <theoretical units="MDa">6.600700000000001e-05</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <formula>BEF</formula>
            </ligand>
            <ligand macromolecule_id="7">
                <name>MAGNESIUM ION</name>
                <molecular_weight>
                    <theoretical units="MDa">2.4305e-05</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <formula>MG</formula>
            </ligand>
            <ligand macromolecule_id="8">
                <name>(3R,4R,5S)-3,4-dihydroxy-5-[(1R,2R,3S,4S,5R,6R,8E,10E,14E,16Z)-1,2,3,4,5-pentahydroxy-6,20,20-trimethylhenicosa-8,10,14,16-tetraen-1-yl]oxolan-2-one</name>
                <molecular_weight>
                    <theoretical units="MDa">0.000526659</theoretical>
                </molecular_weight>
                <number_of_copies>1</number_of_copies>
                <formula>A1BD6</formula>
            </ligand>
        </macromolecule_list>
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            <method>singleParticle</method>
            <aggregation_state>particle</aggregation_state>
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                        <ph>7.4</ph>
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                    <vitrification>
                        <cryogen_name>ETHANE</cryogen_name>
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                    <microscope>TFS KRIOS</microscope>
                    <illumination_mode>FLOOD BEAM</illumination_mode>
                    <imaging_mode>BRIGHT FIELD</imaging_mode>
                    <electron_source>FIELD EMISSION GUN</electron_source>
                    <acceleration_voltage units="kV">300</acceleration_voltage>
                    <nominal_defocus_min units="µm">1.3</nominal_defocus_min>
                    <nominal_defocus_max units="µm">1.7</nominal_defocus_max>
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                        <image_recording image_recording_id="1">
                            <film_or_detector_model>GATAN K3 (6k x 4k)</film_or_detector_model>
                            <average_electron_dose_per_image units="e/Å^2">60.0</average_electron_dose_per_image>
                        </image_recording>
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                <ctf_correction>
                    <type>PHASE FLIPPING AND AMPLITUDE CORRECTION</type>
                </ctf_correction>
                <startup_model type_of_model="INSILICO MODEL"/>
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                    <resolution_method>FSC 0.143 CUT-OFF</resolution_method>
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                    <type>MAXIMUM LIKELIHOOD</type>
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