CRYSTAL STRUCTURE OF MOXIFLOXACIN, DNA, and A. BAUMANNII TOPO IV (PARE-PARC FUSION TRUNCATE)

1-cyclopropyl-6-fluoro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Structural Basis of Quinolone Inhibition of Type Iia Topoisomerases and Target-Mediated Resistance

THE CONSTRUCT IS A FUSION OF THE TOPO IV, PARE AND PARC SUBUNITS. RESIDUE 604 OF PARE IS LINKED TO RESIDUES 996 OF PARC
PARE SUBUNIT C-TERMINAL 28KDA DOMAIN, RESIDUES 370-627, PARC SUBUNIT N-TERMINAL 58KDA DOMAIN, RESIDUES 1 TO 503

DNA CLEAVED INTO 2, COMPLEX TRAPPED BY MFX

MEMAISKAGRRLKAAKKVERKKIVSGPALPGKLADCVGQTREESELFIVEGDSAGGSAKQARDKNFQAIMPIRGKILNTW
EVSSDEVLASQEVHDIAIAIGVDPGSDDLSELRYGKICILADADSDGLHIATLLCALFVKHFPALVEEGHLYVAMPPLFR
IDIGKDVHYALDDEELETILKNVKGNKNPQITRFKGLGEMNAIQLRETTMDPNTRRLVQLDLDDAHLTAGLLDKLLAKKR
AADRKQWLEQKGNLADITVEDKLTMTSLAHHATENRSVAEFTEQAYLNYAMYVIMDRALPHISDGLKPVQRRIVYAMSEL
GLKSSGKPKKSARTVGDVLGKYHPHGDSACYEAMVLMAQPFSYRYPLIEGQGNWGSPDDPKSFAAMR(PTR)TEAKLSAY
SELLLSELGQGTSEWQDNFDGSLKEPITLPARVPNILLNGTTGIAVGMATDIPPHNLREVVKGTIALIRNPQTSDEKLAE
YIPAPDLPTKAEIITPPEELLKIQTTGRGSYRMRAVYTIEKNEIVITELPYQVSGSKVITQIADQMQAKKLPLVVDVRDE
SDHENPTRLVIVLRSNRIDAEAVMSHLFATTDLESSYRVNLNMIGEDGRPQVKSIRRILLEWIEIRKKTVTRRLQYHLNR
IEKRLHILAGLLIAYLDIDTVIRIIREEDQPKPVLMEHFNIDEIQAEAILELKLRHLAKLEEMEIRHEQDELSAKAAIIR
EQLENPESLKNLIISELKEDAKKFGDERRSPIVARAEAVQIKEQDLMPAET

MEMAISKAGRRLKAAKKVERKKIVSGPALPGKLADCVGQTREESELFIVEGDSAGGSAKQARDKNFQAIMPIRGKILNTW
EVSSDEVLASQEVHDIAIAIGVDPGSDDLSELRYGKICILADADSDGLHIATLLCALFVKHFPALVEEGHLYVAMPPLFR
IDIGKDVHYALDDEELETILKNVKGNKNPQITRFKGLGEMNAIQLRETTMDPNTRRLVQLDLDDAHLTAGLLDKLLAKKR
AADRKQWLEQKGNLADITVEDKLTMTSLAHHATENRSVAEFTEQAYLNYAMYVIMDRALPHISDGLKPVQRRIVYAMSEL
GLKSSGKPKKSARTVGDVLGKYHPHGDSACYEAMVLMAQPFSYRYPLIEGQGNWGSPDDPKSFAAMRYTEAKLSAYSELL
LSELGQGTSEWQDNFDGSLKEPITLPARVPNILLNGTTGIAVGMATDIPPHNLREVVKGTIALIRNPQTSDEKLAEYIPA
PDLPTKAEIITPPEELLKIQTTGRGSYRMRAVYTIEKNEIVITELPYQVSGSKVITQIADQMQAKKLPLVVDVRDESDHE
NPTRLVIVLRSNRIDAEAVMSHLFATTDLESSYRVNLNMIGEDGRPQVKSIRRILLEWIEIRKKTVTRRLQYHLNRIEKR
LHILAGLLIAYLDIDTVIRIIREEDQPKPVLMEHFNIDEIQAEAILELKLRHLAKLEEMEIRHEQDELSAKAAIIREQLE
NPESLKNLIISELKEDAKKFGDERRSPIVARAEAVQIKEQDLMPAET

(DA)(DC)(DC)(DA)(DA)(DG)(DG)(DT)(DC)(DA)(DT)(DG)(DA)(DA)(DT)(DG)(DA)(DC)(DT)(DA)
(DT)(DG)(DC)(DA)(DC)(DG)(DT)(DA)(DA)(DA)(DA)(DC)(DA)(DG)

(DC)(DT)(DG)(DT)(DT)(DT)(DT)(DA)(DC)(DG)(DT)(DG)(DC)(DA)(DT)(DA)(DG)(DT)(DC)(DA)
(DT)(DT)(DC)(DA)(DT)(DG)(DA)(DC)(DC)(DT)(DT)(DG)(DG)(DT)

8% PEG 5000MME, 200 MM TRIS PH 8.5, 100 MM MGCL2

CRYSTAL STRUCTURE OF CATALYTIC CORE OF A. BAUMANNII TOPO IV (PARE-PARC FUSION TRUNCATE)

((CHAIN A AND (RESID 385:503 OR RESID 539:567)))

((CHAIN A AND (RESID 569:596)) OR ((CHAIN A) AND (RESID 1013:1026)))

((CHAIN A AND (RESID 1368:1378)) OR (CHAIN A AND (RESID 1439:1455)))

((CHAIN C AND (RESID 1368:1378)) OR (CHAIN C AND (RESID 1439:1455)))

((CHAIN C AND (RESID 385:503 OR RESID 539:567)))

((CHAIN C AND (RESID 569:596)) OR ((CHAIN C) AND (RESID 1013:1026)))

ISOMERASE-DNA-ANTIBIOTIC COMPLEX, TYPE IIA TOPOISOMERASE, QUINOLONE, ANTIBACTERIAL AGENT