The X-Ray Structure of the Ligand-Free Antibiotic Ristocetin-A Reveals the Role of the Monomer/Dimer Equilibrium in Its Binding Mode

<div>Chemical structure of ristocetin-A. The molecule dimerizes via four intermolecular H bonds (sequence in red). The asymmetric unit is a dimer: <svg height="14.2327pt" id="M1" style="vertical-align:-3.1815pt" version="1.1" viewbox="-0.0498162 -11.0512 82.6322 14.2327" width="82.6322pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M300 -147C201 -63 143 98 143 270S200 602 300 686L282 710C136 610 70 450 70 271V270C70 89 136 -72 282 -170L300 -147Z" id="g113-41"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="346" vert-adv-y="346"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,4.498,0)"><path d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z" id="g190-115"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="371" vert-adv-y="371"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,9.399,0)"><path d="M135 536C164 536 186 560 186 587C186 617 164 639 136 639C109 639 85 617 85 587C85 560 109 536 135 536ZM252 0V26C188 32 181 38 181 106V451C138 433 90 420 39 412V388C99 379 102 374 102 312V106C102 38 95 32 32 26V0H252Z" id="g190-106"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="268" vert-adv-y="268"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,12.844,0)"><path d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z" id="g190-116"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="367" vert-adv-y="367"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,17.55,0)"><path d="M298 36L289 62C276 55 253 45 228 45C202 45 169 60 169 141V397H276C289 405 292 426 282 437H169V574L155 576L90 509V437H45L17 408L21 397H90V107C90 28 125 -12 188 -12C198 -12 213 -8 230 1L298 36Z" id="g190-117"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="305" vert-adv-y="305"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,21.437,0)"><path d="M257 449C165 449 37 374 37 209C37 98 119 -12 256 -12C355 -12 473 65 473 226C473 349 381 449 257 449ZM244 416C333 416 380 320 380 204C380 67 329 21 267 21C184 21 130 115 130 241C130 354 184 416 244 416Z" id="g190-112"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="510" vert-adv-y="510"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,28.184,0)"><path d="M390 111C344 68 312 56 269 56C212 56 118 102 118 241C118 346 175 401 241 401C277 401 312 388 342 360C350 352 355 349 361 349C372 349 394 371 394 392C394 403 391 411 378 422C362 436 329 449 288 449H287C250 449 190 432 138 392C71 341 37 274 37 197C37 90 112 -12 238 -12C297 -12 363 32 407 90L390 111Z" id="g190-100"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="423" vert-adv-y="423"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,33.683,0)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z" id="g190-102"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="425" vert-adv-y="425"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,39.208,0)"><path d="M298 36L289 62C276 55 253 45 228 45C202 45 169 60 169 141V397H276C289 405 292 426 282 437H169V574L155 576L90 509V437H45L17 408L21 397H90V107C90 28 125 -12 188 -12C198 -12 213 -8 230 1L298 36Z" id="g190-117"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="305" vert-adv-y="305"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,43.238,0)"><path d="M135 536C164 536 186 560 186 587C186 617 164 639 136 639C109 639 85 617 85 587C85 560 109 536 135 536ZM252 0V26C188 32 181 38 181 106V451C138 433 90 420 39 412V388C99 379 102 374 102 312V106C102 38 95 32 32 26V0H252Z" id="g190-106"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="268" vert-adv-y="268"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,46.722,0)"><path d="M524 0V26C466 32 460 36 460 104V297C460 393 411 449 331 449C302 449 276 437 248 419C223 402 201 387 181 372V451C137 432 90 420 42 411V388C96 378 102 374 102 310V104C102 38 97 33 29 26V0H246V26C187 32 181 36 181 104V339C211 365 250 390 290 390C357 390 381 345 381 276V109C381 40 374 32 315 26V0H524Z" id="g190-111"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="547" vert-adv-y="547"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,53.833,0)"><path d="M300 253H71L57 198H286L300 253Z" id="g190-46"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="356" vert-adv-y="356"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,57.757,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z" id="g190-66"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="691" vert-adv-y="691"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,66.975,0)"><path d="M275 270C275 450 212 609 64 710L45 686C145 604 203 442 203 270S147 -63 45 -147L64 -170C213 -68 275 89 275 270Z" id="g113-42"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="346" vert-adv-y="346"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,71.473,3.132)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z" id="g50-51"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,76.454,-5.996)"><path d="M556 236V289H337V504H275V289H56V236H275V-4H337V236H556Z" id="g54-36"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g></svg>, <svg height="14.7729pt" id="M2" style="vertical-align:-3.181499pt" version="1.1" viewbox="-0.0498162 -11.5914 31.5059 14.7729" width="31.5059pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M409 504C401 567 396 607 392 642C354 654 312 665 266 665C137 665 60 583 60 487C60 374 161 325 225 290C300 250 355 215 355 141C355 68 311 21 235 21C131 21 86 122 71 183L41 176C48 128 61 42 68 21C78 16 93 8 118 0C142 -7 175 -15 216 -15C349 -15 438 69 438 174C438 287 344 333 265 374C186 414 138 449 138 522C138 576 172 631 249 631C336 631 363 562 380 499L409 504Z" id="g121-81"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="474" vert-adv-y="474"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,6.162,0)"><path d="M381 665C170 665 44 498 44 318C44 125 188 -15 369 -15C552 -15 703 117 703 333C703 534 550 665 381 665ZM359 629C491 629 601 517 601 306C601 114 502 21 390 21C249 21 146 158 146 346S248 629 359 629Z" id="g121-77"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="747" vert-adv-y="747"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,15.932,3.132)"><path d="M462 177V227H365V632H320C217 496 116 350 21 208V177H284V109C284 43 280 38 190 31V0H451V31C369 38 365 43 365 108V177H462ZM284 227H88C155 336 218 430 282 519H284V227Z" id="g50-53"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,20.879,-5.741)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z" id="g50-51"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,25.311,-5.741)"><path d="M556 236V289H56V236H556Z" id="g54-33"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g></svg>. The amino-acid configurations are DDLDDLL from residues #1 to #7, respectively. The tetrasaccharide Rha-Glc-Man-Ara is represented in the<i> anti </i>orientation with respect to the glycosidic bond Glc-Tyr 4, that is, positioning the arabinose sugar near the glycosylated <i>β</i>-Tyr 6 residue.</div>

Journal of Crystallography

fig1

Figure 1

Figure 1: The X-Ray Structure of the Ligand-Free Antibiotic Ristocetin-A Reveals the Role of the Monomer/Dimer Equilibrium in Its Binding Mode 