Jump to content

  • Log in with Facebook Log in with Twitter Log in with Windows Live Log In with Google      Sign In   
  • Create Account

Submit your paper to J Biol Methods today!
Photo
- - - - -

Human homologs, orthologs, and paralogs for bacterial topoisomerases

homologs orthologs paralogs topoisomerases bacterial

  • Please log in to reply
3 replies to this topic

#1 BuildingHealth

BuildingHealth

    member

  • Members
  • Pip
  • 2 posts
0
Neutral

Posted 22 February 2014 - 08:31 AM

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?
NAME: Levaquin
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 B)
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 B)
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


#2 bob1

bob1

    Thelymitra pulchella

  • Global Moderators
  • PipPipPipPipPipPipPipPipPipPip
  • 5,603 posts
385
Excellent

Posted 22 February 2014 - 12:54 PM

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.



#3 BuildingHealth

BuildingHealth

    member

  • Members
  • Pip
  • 2 posts
0
Neutral

Posted 22 February 2014 - 05:11 PM

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?



#4 bob1

bob1

    Thelymitra pulchella

  • Global Moderators
  • PipPipPipPipPipPipPipPipPipPip
  • 5,603 posts
385
Excellent

Posted 22 February 2014 - 11:04 PM

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.







Also tagged with one or more of these keywords: homologs, orthologs, paralogs, topoisomerases, bacterial

Home - About - Terms of Service - Privacy - Contact Us

©1999-2013 Protocol Online, All rights reserved.