Human homologs, orthologs, and paralogs for bacterial topoisomerases - (Feb/22/2014 )
Literature suggests that neuropathy, nephrotoxicity as well as damage to cartilage and tendons are the most common severe (though reportedly rare) side-effects of Levofloxacin.
I apologize for not having a more expansive vocabulary yet, so as to frame my question more precisely.
My limited understanding is that Levofloxacin induces double-strand breaks for the targeted pathogens.
My further limited understanding is that we have genetics in common with all organisms, at least on some level.
So, the question then is:
- What homo sapiens homologs, orthologs or paralogs are there for these targeted bacterial topoisomerases?
PSUEDONYM: Levofloxacin
COMPANY: Ortho-McNeil Pharmaceuticals
TREATS: Bacterial infections
THERAPEUTIC AREA: Anti-infectives
CHEMICAL FAMILY: Quinolone antibiotic
MECHANISM: Stops supercoiling of bacterial DNA
MECHANISM_MORE: The mechanism of action of levofloxacin and other fluoroquinolone
antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase
(both of which are type II topoisomerases), enzymes required for DNA replication,
transcription, repair and recombination. (prescribing information)
TARGET: Topoisomerase II (DNA gyrase A) and IV (DNA gyrase
TARGET_IDS: Q8XE30 | Q8FDI7 + Q8XBQ4
TARGET_CLASS: Enzyme
TISSUE: N/A
CELLULAR_LOCATION: N/A
REVIEW1:
PATHWAY: DNA replication
STRUCTURE: 1ab4 E.coli Top II (DNA Gyrase A) & 1eil E. coli Top IV (DNA Gyrase
CAS_RN: 100986-85-4
ACX_NUMBER: X1012954-5
SEQUENCES:
>uniprot|Q8XE30|Q8XE30 DNA gyrase, subunit A, type II topoisomerase.
MSDLAREITPVNIEEELKSSYLDYAMSVIVGRALPDVRDGLKPVHRRVLYAMNVLGNDWN
KAYKKSARVVGDVIGKYHPHGDSAVYDTIVRMAQPFSLRYMLVDGQGNFGSIDGDSAAAM
RYTEIRLAKIAHELMADLEKETVDFVDNYDGTEKIPDVMPTKIPNLLVNGSSGIAVGMAT
NIPPHNLTEVINGCLAYIDDEDISIEGLMEHIPGPDFPTAAIINGRRGIEEAYRTGRGKV
YIRARAEVEVDAKTGRETIIVHEIPYQVNKARLIEKIAELVKEKRVEGISALRDESDKDG
MRIVIEVKRDAVGEVVLNNLYSQTQLQVSFGINMVALHHGQPKIMNLKDIIAAFVRHRRE
VVTRRTIFELRKARDRAHILEALAVALANIDPIIELIRHAPTPAEAKTALVANPWQLGNV
AAMLERAGDDAARPEWLEPEFGVRDGLYYLTEQQAQAILDLRLQKLTGLEHEKLLDEYKE
LLDQIAELLRILGSADRLMEVIREELELVREQFGDKRRTEITANSADINLEDLITQEDVV
VTLSHQGYVKYQPLSEYEAQRRGGKGKSAARIKEEDFIDRLLVANTHDHILCFSSRGRVY
SMKVYQLPEATRGARGRPIVNLLPLEQDERITAILPVTEFEEGVKVFMATANGTVKKTVL
TEFNRLRTAGKVAIKLVEGDELIGVDLTSGEDEVMLFSAEGKVVRFKESSVRAMGCNTTG
VRGIRLGEGDKVVSLIVPRGDGAILTATQNGYGKRTAVAEYPTKSRATKGVISIKVTERN
GLVVGAVQVDDCDQIMMITDAGTLVRTRVSEISIVGRNTQGVILIRTAEDENVVGLQRVA
EPVDEEDLDTIDGSAAEGDDEIAPEVDVDDEPEEE
>uniprot|Q8XBQ4|Q8XBQ4 DNA topoisomerase IV subunit B.
MTQTYNADAIEVLTGLEPVRRRPGMYTDTTRPNHLGQEVIDNSVDEALAGHAKRVDVILH
ADQSLEVIDDGRGMPVDIHPEEGVPAVELILCRLHAGGKFSNKNYQFSGGLHGVGISVVN
ALSKRVEVNVRRDGQVYNIAFENGEKVQDLQVVGNCGKRNTGTSVHFWPDETFFDSPRFS
VSRLTHVLKAKAVLCPGVEITFKDEINNTEQRWCYQDGLNDYLAEAVNGLPTLPEKPFIG
NFAGDTEAVDWALLWLPEGGELLTESYVNLIPTMQGGTHVNGLRQGLLDAMREFCEYRNI
LPRGVKLSAEDIWDRCAYVLSVKMQDPQFAGQTKERLSSRQCAAFVSGVVKDAFILWLNQ
NVQAAELLAEMAISSAQRRMRAAKKVVRKKLTSGPALPGKLADCTAQDLNRTELFLVEGD
SAGGSAKQARDREYQAIMPLKGKILNTWEVSSDEVLASQEVHDISVAIGIDPDSDDLSQL
RYGKICILADADSDGLHIATLLCALFVKHFRALVKHGHVYVALPPLYRIDLGKEVYYALT
EEEKEGVLEQLKRKKGKPNVQRFKGLGEMNPMQLRETTLDPNTRRLVQLTIDDEDDQRTD
AMMDMLLAKKRSEDRRNWLQEKGDMAEIEV
>uniprot|Q8FDJ9|Q8FDJ9 Topoisomerase IV subunit A (EC 5.99.1.-).
MSDMAERLALHEFTENAYLNYSMYVIMDRALPFIGDGLKPVQRRIVYAMSELGLNASAKF
KKSARTVGDVLGKYHPHGDSACYEAMVLMAQPFSYRYPLVDGQGNWGAPDDPKSFAAMRY
TESRLSKYSELLLSELGQGTADWVPNFDGTLQEPKMLPARLPNILLNGTTGIAVGMATDI
PPHNLREVAQAAIALIDQPKTTLDQLLDIVQGPDYPTEAEIITSRAEIRKIYENGRGSVR
MRAVWKKEDGAVVISALPHQVSGARVLEQIAAQMRNKKLPMVDDLRDESDHENPTRLVIV
PRSNRVDMDQVMNHLFATTDLEKSYRINLNMIGLDGRPAVKNLLEILSEWLVFRRDTVRR
RLNYRLEKVLKRLHILEGLLVAFLNIDEVIEIIRNEDEPKPALMSRFGLTETQAEAILEL
KLRHLAKLEEMKIRGEQSELEKERDQLQGILASERKMNNLLKKELQADAQAYGDERRSPL
QEREEAKAMSEHDMLPSEPVTIVLSQMGWVRSAKGHDIDAPGLNYKAGDSFKAAVKGKSN
QPVVFVDSTGRSYAIDPITLPSARGQGEPLTGKLTLPPGATVDHMLMESDDQKLLMASDA
GYGFVCTFNDLVARNRAGKALITLPENAHVMPPVVIEDASDMLLAITQAGRMLMFPVSDL
PQLSKGKGNKIINIPSAEAARGEDGLAQLYVLPPQSTLTIHVGKRKIKLRPEELQKVTGE
RGRRGTLMRGLQRIDRVEIDSPRRASSGDSEE
>uniprot|Q8FDI7|Q8FDI7 Topoisomerase IV subunit B (EC 5.99.1.-).
MTQTYNADAIEVLTGLEPVRRRPGMYTDTTRPNHLGQEVIDNSVDEALAGHAKRVDVILH
ADQSLEVIDDGRGMPVDIHPEEGVPAVELILCRLHAGGKFSNKNYQFSGGLHGVGISVVN
ALSKRVEVNVRRDGQIYNIAFENGEKVQDLQVVGTCGKRNTGTSVHFWPDETFFDSPRFS
VSRLTHVLKAKAVLCPGVEITFKDEINNTEQRWCYQDGLNDYLAEAVNGLPTLPEKPFIG
NFAGDTEAVDWALLWLPEGGELLTESYVNLIPTMQGGTHVNGLRQGLLDAMREFCEYRNI
LPRGVKLSAEDIWDRCAYVLSVKMQDPQFAGQTKERLSSRQCAAFVSGVVKDAFILWLNQ
NVQAAELLAEMAISSAQRRMRAAKKVVRKKLTSGPALPGKLADCTAQDLNRTELFLVEGD
SAGGSAKQARDREYQAIMPLKGKILNTWEVSSDEVLASQEVHDISVAIGIDPDSDDLSQL
RYGKICILADADSDGLHIATLLCALFVKHFRALVKHGHVYVALPPLYRIDLGKEVYYALT
EEEKEGVLEQLKRKKGKPNVQRFKGLGEMNPMQLRETTLDPNTRRLVQLTIDDEDDQRTD
AMMDMLLAKKRSEDRRNWLQEKGDMAEIEV
AFAIK, eukaryotes use the same topoisomerases as bacteria (google it for yourself) - I suspect like most of these sorts of things it is the rate of replication that is important.
Thank you for your reply. Would you please explain like I'm five why you suspect that it is the rate of replication that is important?
Are you referencing within the human body, or in killing bacteria?
Rate of replication of both - bacteria replicate very fast (typically, depends on the species and conditions) in the human body, usually a few times per hour. Human cells replicate slowly, even the fastest cancer lines replicate only about once per 18 hours, so the rate of accumulation of double strand breaks is low in human cells, but high in bacteria... hence bacteria get killed and human cells not so much.
I want to upload the complete parameterset of a ATV66 and a ATV452 inverter. Schneider Electric says the original software for these inverters is no longer available. Can anyone get me the original commissioning software? Or is there an other way to do it? Thank you very much, Jo
You are in the wrong place @Danfosvltsrew (Jo)... this is a biomedical forum, not a software source.