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It is made available under aCC-BY-NC-ND 4.0 International license. )LJ7KHVFKHPHRIIUDJPHQWDWLRQRI6'63$*(VODEVIRU0606DQDO\VLV7KH6'63$*( VODE VKRZQ LQ WKH ILJXUH H[HPSOLILHV WKH ODQHV ORDGHG ZLWK SURWHLQV REWDLQHG LQ FURVVOLQNLQJ H[SHULPHQWVZLWK+/0 /)- XVLQJ%30&<3( DQG%36&<3( DVDEDLWSURWHLQDQG D FRQWURO H[SHULPHQW ZLWK WKH VDPH PLFURVRPHV VXEMHFWHG WR LQFRUSRUDWLRQ DQG LVRODWLRQ RI XQODEHOHG&<3( /DQHVDQGFRUUHVSRQGWRWKHFDOLEUDWLQJSURWHLQODGGHU DQGN'$ DQGWKHSXULILHG&<3(SURWHLQUHVSHFWLYHO\ bioRxiv preprint was notcertifiedbypeerreview)istheauthor/funder,whohasgrantedbioRxivalicensetodisplaypreprintinperpetuity.Itmade doi: https://doi.org/10.1101/2021.07.02.450960 available undera CC-BY-NC-ND 4.0Internationallicense ; this versionpostedJuly3,2021. The copyrightholderforthispreprint(which . )LJ'LVWULEXWLRQRISRWHQWLDOO\FURVVOLQNHGSURWHLQVEHWZHHQWKHLQGLYLGXDOEDQGVRIWKH6'63$*(ODQHVREWDLQHGLQWKHH[SHULPHQWV ZLWK%30&<3( $ DQG%36&<3( % 7KHGDWDVKRZQLQWKHJUDSKUHSUHVHQWWKHDYHUDJHVRIWKUHHLQGLYLGXDOH[SHULPHQWVZLWK+/0 /)- DQG+/0 /%$ VXPPDUL]HGLQ7DEOH7KH<D[LVRIWKHSORWFRUUHVSRQGVWRWKHUDWLRRIQRUPDOL]HGDSSDUHQWSURWHLQDEXQGDQFHLQWKHFURVVOLQNHG VDPSOHWRWKDWREVHUYHGLQWKHFRQWURO2UGLQDWHRIWKHJUDSKVKRZVWKHDSSUR[LPDWHDYHUDJHGPROHFXODUZHLJKWVRIDOOSURWHLQVIRXQGLQHDFKEDQG bioRxiv preprint doi: https://doi.org/10.1101/2021.07.02.450960; this version posted July 3, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Table 1. Results of six individual CXMS experiments* Crosslinkimg with BPM Crosslinking with BPS HLM(LFJ), assay 1 HLM(LFJ), assay 2 HLM(LBA) HLM(LFJ), assay 1 HLM(LFJ), assay 2 HLM(LBA) Total Protein positives 55 75 100 140 180 55 75 100 140 180 55 75 100 140 180 55 75 100 140 180 55 75 100 140 180 55 75 100 140 180 kDA a kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA kDA CYP2E1 1.3 1.8 0.3 1.9 3.0 0.6 0.8 1.1 1.6 1.9 0.9 1.7 0.5 1.0 0.5 1.5 1.7 0.3 1.4 3.1 0.5 0.8 1.3 1.6 2.0 0.5 4.4 0.7 0.8 0.4 0 CYP1A2 0.7 0.8 245 0 0 0.7 1.8 1.5 0 0 0.7 0 0 0 1.1 0.7 0 0 0 0.5 2.5 2.0 0 0 0 0 0 0 3 CYP2A6 b 0.4 0.7 486 0.6 0 0.3 0.9 1.9 0 0 0.1 50 17.6 18.0 0 0.7 0.6 306 1.0 0 0.6 1.0 1.1 83 0 0.1 25 23 19 26 5 CYP2B6 0.6 206 207 0 0 82 294 624 0 0 0 0 0 0 0 1.0 0 0 0 0 125 260 0 0 0 0 0 0 0 3 CYP2C18 0.9 0 0 0 0 0.4 554 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 CYP2C19 0.7 1.9 147 0.5 105 0.8 0.7 2.4 107 0 0 0 0 0 0 0.7 3.0 279 0.3 0 0.4 1.0 2.9 167 0 0 0 0 0 0 4 CYP2C8 1.6 1.4 1.0 0.3 0.7 0.8 0.5 3.2 1.0 0.9 0.4 13 6.6 0 0 1.9 0.6 1.0 0.4 1.9 0.5 0.4 3.4 0.8 3.5 0.1 8.5 4.7 3 8.3 1 CYP2C9 1.0 2.2 206 0.3 0 0.8 1.5 2.0 0.6 0 0.6 19 4.7 3.2 0 0.8 2.9 238 0.3 0 0.4 2.7 2.1 0.9 73 0.3 36 6.8 2 4.6 5 CYP2D6 1.2 0.5 0 0 0 0.3 245 432 0 0 1.0 0 0 0 0 1.4 0.1 0 0 0 0.3 334 345 0 0 0 0 0 0 3 CYP3A4c 0.7 1.9 226 0.6 0 0.6 1.9 1.2 1.0 0 0.5 50 3.3 0 0 0.9 1.5 244 0.4 0.4 0.4 1.8 1.2 0.8 150 0 74 7.6 0 14 5 CYP3A5 1.2 119 150 0.7 0 1.0 288 0.7 0.8 0 0 0 0 0 0 2.0 0 194 0.2 0 0 413 1.9 0.7 0 0 0 0 0 0 4 CYP4A11d 0.5 1.4 257 0.5 0 0.5 3.2 11 0.4 0 0.6 22 0 0 0 1.1 0.7 51 0 0 0.3 2.7 17 0 0 0.2 37 2.4 0 0 6 CYP4F12 0.7 254 91 0 0 0.8 0.6 195 0 0 1.0 0 0 0 0 1.0 0 0 0 0 0.7 1.4 165 0 0 0 0 0 0 0 3 CYP4F2 0.7 1.1 174 1.0 0 0.7 1.4 152 0.8 0 1.2 1.6 0 0 0 1.0 0 213 0.5 0 0.6 1.7 180 0.3 180 1.2 2.1 0 0 0 4 CYP4F8 0.2 229 0 0 0.8 249 0 0 0 0 0 0 0 0 0 0 0 0 0.6 239 188 0 0 0 0 0 0 4 CYB5A 0 1.0 0 0 0 229 226 0 0 0 0 0 0 0 127 0.9 0 0 0 220 306 316 0 158 0 0 0 0 0 2 NCPR 1.4 1.2 0.4 0.7 0 2.2 0.7 1.7 1.7 0 8.5 336 2.0 0 0 2.1 1.0 0.5 1.3 0 3.4 0.6 1.5 1.7 39 18 56 36 0 1 2 PGRMC1 0 1.0 0 0 0 0 1.0 0 0 0 0 0 0 0 0 225 0.8 0 0 0 385 0.5 140 0 0 0 0 0 0 0 2 UGT1A1 1.0 1.0 153 0.6 0 0.8 1.6 1.2 1.0 0 1.0 0 0 0 0 0.5 1.4 367 0.5 0 0.6 1.0 1.1 0.8 175 0 0 0 0 4 UGT1A3 0.9 0.7 178 0 0 0.6 364 0 0 0 1.0 0 0 0 0 1.3 0 0 0 0 0.5 203 325 0 0 0 0 0 0 0 3 UGT 1A4 e 0.9 0.8 133 0.5 76 0.6 1.1 1.6 1.8 0 1.0 0 0 0 0 0.6 1.4 370 0.3 0 0.7 0.9 2.0 1.0 97 0.5 47 0 0 0 4 UGT 1A6 0.9 0.7 157 0.5 72 0.4 2.2 2.6 1.2 50 0.7 0 2.0 0 0.7 1.2 203 0.6 0 0.6 2.2 2.1 0.8 89 0.6 21 6.0 4 5.3 6 UGT 1A9f 0.7 110 132 0.9 0 0.4 236 246 111 0 0.5 5.3 1.0 0 0.6 220 214 0.5 0 0.4 218 312 92 0 0.3 38 5.9 1 15 6 UGT 2A1 0.7 115 216 0 0 1.2 0 0.7 0 0 0 0 0 0 0 1.0 0 0 0 0 1.0 0 1.0 0 0 0 0 0 0 0 1 UGT2A3 1.0 0 0 0 0 1.0 0 0 0 0 1.0 0 0 0 0 1.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 UGT 2B10 0.5 1.6 223 1.2 1.1 0.5 1.4 1.2 1.9 3.7 0.6 0 0 0 0.6 1.6 112 0.9 1.9 0.4 1.0 1.2 1.3 7.5 0 0 0 0 4 UGT 2B11 0.4 0.8 268 0.9 102 0.6 0.9 0.8 131 137 0 0 0 0 0 1.4 1.5 0 0 0 0.5 0.4 0.8 0 428 0 0 0 0 0 3 UGT 2B15 0.5 0.6 215 1.4 2.5 0.5 2.5 0.6 1.5 181 0.6 0 0 0 0.8 1.0 226 0.7 0 0.5 2.5 0.7 0.6 287 0 0 0 0 0 5 UGT 2B17 1.0 1.2 249 0 1.4 0.5 1.1 0.8 1.4 195 0.5 27 8.3 6.5 0 1.1 1.3 267 0.4 0 0.5 1.1 0.9 0.8 256 0 45 6.8 13 15 6 UGT 2B28 0.6 1.4 335 0 1.9 0.6 0.8 1.0 1.2 188 0 0 0 0 0 1.5 0.7 120 0.2 0 0.3 0.9 1.4 0.2 437 0 0 0 0 0 4 UGT 2B4 0.5 1.1 287 0.9 0.8 0.6 2.2 0.8 1.7 120 0.7 7.7 1.7 8.1 0 0.8 1.0 217 0.6 0.8 0.4 1.6 1.0 1.2 237 0.4 18 0 18 0 5 UGT 2B7 0.5 0.7 212 1.0 1.7 0.6 1.3 1.1 1.1 3.2 0.7 14 3.8 7.6 0 0.5 0.7 230 0.9 1.5 0.4 1.1 1.1 1.2 4.9 0.1 38 8.6 9.2 17 4 CES1 1.9 1.7 0.2 1.4 2.3 1.0 0.8 0.8 0.9 1.6 3.5 1.2 0.7 0.6 0.1 1.2 1.5 0.3 1.5 3.1 1.0 0.8 1.0 1.1 1.1 2.1 2.7 1.1 0.4 1.7 0 P4HB 1.0 1.4 0.3 2.5 3.3 0.7 1.0 1.3 1.3 2.4 0.8 11 6.3 0.8 2.6 0.7 1.3 0.4 2.2 5.3 0.5 0.8 1.5 1.8 2.7 0.5 28 9.7 0.8 15 2 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.02.450960; this version posted July 3, 2021. 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