SQUALENE
MONOOXYGENASE AND RELATED FLAVOPROTEINS
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Squalene
monooxygenase bears little sequence similarity to other
flavoproteins. Nonetheless, it is likely to be related to other
FAD-containing monooxygenases, the best studied of which is p-hydroxybenzoate
hydroxylase. The 3-dimensional structure of this enzyme is known,
and serves as a model for all FAD monooxygenases.
There are
currently (as of October 2001) 9 complete squalene monooxygenase
sequences known, as shown in the table below:
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Alignment of
Squalene Monooxygenase Sequences
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Squalene
monooxygenases exhibit several segments of sequence conservation,
suggesting conservation of function in these segments. In the
alignment of squalene monooxygenase sequences shown below, the sequence
highlighted in blue
indicates the likely membrane binding segment of the mammalian
enzymes. Although all squalene monooxygenases are thought to be
membrane-bound (to the endoplasmic reticulum), the mechanism of binding
for the yeast and plant enzymes is not known.
 Although
squalene monooxygenases exhibit little overall sequence similarity to
other flavoproteins, careful examination of the sequences reveals some
segments of similarity. Based on comparisons with several conserved
flavin-binding sequence motifs present in a variety of flavoproteins, the
three sequences highlighted in yellow
below are likely to be involved in binding the FAD (flavin) group of
squalene monooxygenase. The first
sequence contains
a typical "Rossman fold" sequence (GxGxxG) that binds
dinucleotide pyrophosphate groups. The second
sequence was recently identified in a
variety of flavoprotein monooxygenases, and may also be involved in
binding the FAD pyrophosphate moiety, as well as the NADPH cofactor in
some enzymes (Eppink
et al., Protein Sci. 6, 2454-2458, 1997). However,
mutations in rat squalene monooxygenase at three of the most conserved
amino acids in this sequence impaired activity but did not affect the Km
of FAD (Lee
et al., Arch. Biochem. Biophys. 381, 43-52, 2000).
The third
sequence has
been identified in a wide variety of flavoproteins and is thought to
interact with the ribityl portion of the flavin molecule (Eggink
et al., J. Mol. Biol. 212, 135-142,
1990). Mutations in rat squalene monooxygenase at either of the
two most conserved amino acids in this sequence (G407 and D408) resulted
in >50% loss of activity and 6-12-fold increases in the Km for FAD,
consistent with a role for this segment in FAD binding (Lee
et al., Arch. Biochem. Biophys. 381, 43-52, 2000).
See the Key
below the alignment for explanation of abbreviations.
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SE_Ath
~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
SE_Bna ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_Pgi ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_mus MWTFLGIATF TYFYKKCGD. VTLANKELLL
CVLVFLSLGL VLSYRCRHRH
SE_rat MWTFLGIATF TYFYKKCGD. VTLANKELLL
CVLVFLSLGL VLSYRCRHRN
SE_hum MWTFLGIATF TYFYKKFGDF ITLANREVLL
CVLVFLSLGL VLSYRCRHRN
SE_Cal ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_Sce ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_Spo ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
Consensus MWTFLGIATF TYFYKKCGD- VTLANKELLL
CVLVFLSLGL VLSYRCRHRN
SE_Ath ~~~~~~~~~~ ~~~~~~~~~~ ~~~FTNVCLW
TLLAFMLTWT VFYVTNRGKK
SE_Bna ~~~~~~~~~~ ~~~~~~~~~M DLAFPHVCLW
TLLAFVLTWT VFYVNNRRKK
SE_Pgi MNSSSSTTTT DTLHSFMEAS ALLIDQYFLG
WIFAFLFGFL LLLNFKRKRE
SE_mus GGLLGRHQSG AQFAAFSDIL SALPLIGFFW
AKS.PESEKK EQLESKKCRK
SE_rat GGLLGRHQSG SQFAAFSDIL SALPLIGFFW
AKSPPESEKK EQLESKRRRK
SE_hum GGLLGRQQSG SQFALFSDIL SGLPFIGFFW
AKSPPESENK EQLEARRRRK
SE_Cal ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_Sce ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
SE_Spo ~~~~~~~~~~ ~~~~~~~~~~ ~~~~~~~~~~
~~~~~~~~~~ ~~~~~~~~~~
Consensus GGLLGR-QSG -QFA-FSDIL S-LP-I-F-W
---------- --L---R-RK
SE_Ath ATQLADAVVE ERED...... ..GATDVIIV
GAGVGGSALA
YALAKDGRRV
SE_Bna VAKLPDAATE VRRD...... ..GDADVIIV
GAGVGGSALA
YALAKDGRRV
SE_Pgi KNNSTEFGTD DSNGYYTPEN IAGSTDVIIV
GAGVAGSALA
YTLANDGRRV
SE_mus EIGLSETTLT GAATSVSTSF VT.DPEVIIV
GSGVLGSALA
AVLSRDGRKV
SE_rat EVNLSETTLT GAATSVSTSS VT.DPEVIII
GSGVLGSALA
TVLSRDGRTV
SE_hum GTNISETSLI GTAACTSTSS QN.DPEVIIV
GAGVLGSALA
AVLSRDGRKV
SE_Cal ~~~~~~~~~~ ~~~~~~~~~M SSVKYDAIII
GAGVIGPTIA
TAFARQGRKV
SE_Sce ~~~~~~MSAV NVAPELINAD NTITYDAIVI
GAGVIGPCVA
TGLARKGKKV
SE_Spo ~~~~~~~~~~ ~~~~~~~~~M ATQDADIIII
GAGITGCALG
AALGRQGRKV
Consensus ---L-E---- ---------- -----DVIIV
GAGVLGSALA --LARDGRKV
SE_Ath HVIERDLREP
ERIMGEFMQP GGRLMLSKLG LEDCLEGIDA QKATGMTVYK
SE_Bna HVIERDMREP
VRMMGEFMQP GGRLLLSKLG LEDCLEGIDE QIATGLAVYK
SE_Pgi HVIERDLTEQ
DRIVGELLQP GGYLKLIELG LEDCVNEIDA QRVFGYALYM
SE_mus TVIERDLKEP
DRIVGELLQP GGYRVLQELG LGDTVEGLNA HHIHGYIVHD
SE_rat TVIERDLKEP
DRILGECLQP GGYRVLRELG LGDTVESLNA HHIHGYVIHD
SE_hum TVIERDLKEP
DRIVGEFLQP GGYHVLKDLG LGDTVEGLDA QVVNGYMIHD
SE_Cal LIVERDWSKP
DRIVGELMQP AGIKALRELG MIKAINNIRA VDCTGYYIKY
SE_Sce LIVERDWAMP
DRIVGELMQP GGVRALRSLG MIQSINNIEA YPVTGYTVFF
SE_Spo
LVLERDMSEP DRIVGELLQP
GGIEALEKIG IADAVEGIDG QWTSGYQIFY
Consensus -VIERDL-EP
DRIVGELLQP GG---L--LG L-D-VEGIDA Q---GY----
SE_Ath DGKEAVASFP .......... ..........
.......... ....VDNNNF
SE_Bna DGQKALVSFP .......... ..........
.......... ....ED.NDF
SE_Pgi DGKNTRLSYP .......... ..........
.......... ....LEK..F
SE_mus YESRSEVQIP YPLSE..... .......... ...TNQVQS.
..........
SE_rat CESRSEVQIP YPVSE..... .......... ...NNQVQS.
..........
SE_hum QESKSEVQIP YPLSE..... .......... ...NNQVQS.
..........
SE_Cal YD..ETITIP YPLKKDACIT NPVKPVPDAV
DGVNDKLDSD STLNVDDWDF
SE_Sce NG..EQVDIP YPYKAD...I PKVEKLKDLV
KDGNDKVLED STIHIKDYED
SE_Spo GD..SNVSVP YPSKPN.... ..........
.......... ..........
Consensus ------V-IP YP-------- ----------
---------- ----------
SE_Ath PFDPSARSFH NGRFVQRLRQ KASSLPNVRL
EEGTVKSLIE ...EKGVIKG
SE_Bna PYEPTGRAFY NGRFVQRLRQ KASSLPTVQL
EEGTVKSLIE ...EKGVIKG
SE_Pgi HSDVAGRSFH NGRFVQRMRE KAASLPNVRM
EQGTVTSLVE ...KKGSVKG
SE_mus .....GIAFH HGRFIMSLRK AAMAEPNVKF
IEGVVLQLLE ...EDDAVIG
SE_rat .....GVAFH HGKFIMSLRK AAMAEPNVKF
IEGVVLRLLE ...EDDAVIG
SE_hum .....GRAFH HGRFIMSLRK AAMAEPNAKF
IEGVVLQLLE ...EDDVVMG
SE_Cal DERVRGAAFH HGDFLMNLRQ ICRDEPNVTA
VEATVTKILR DPSDPNTVIG
SE_Sce DERERGVAFV HGRFLNNLRN ITAQEPNVTR
VQGNCIEILK D..EKNEVVG
SE_Spo GGAYQGIGFH YGRFVMNLRK ALTSTPNVTV
TEATVNELLR DE.TGEVITG
Consensus -----G-AFH HGRF-M-LR- -A--EPNV--
-EGTV--LLE ---E---V-G
SE_Ath VTYKNSA.GE ETTALAPLTV VCDGCYSNLR
RSLNDNNA.E VLSYQVGFIS
SE_Bna VTYKNSA.GE ETTAFAPLTV VCDGCYSNLR
RSVNDNNA.E VISYQVGYVS
SE_Pgi VQYKTKD.GQ ELSAFAPLTI VCDGCFSNLR
RSLCNPKV.E VPSCFVGLIL
SE_mus VQYKDKETGD TKELHAPLTV VADGLFSKFR
KSLISSKV.S VSSHFVGFLM
SE_rat VQYKDKETGD TKELHAPLTV VADGLFSKFR
KNLISNKV.S VSSHFVGFIM
SE_hum VQYKDKETGD IKELHAPLTV VADGLFSKFR
KSLVSNKV.S VSSHFVGFLM
SE_Cal VQTK.QPSGT V.DYHAKLTI SCDGIYSKFR
KELSPTNVPT IGSYFIGLYL
SE_Sce AKVDIDGRGK V.EFKAHLTF ICDGIFSRFR
KELHPDHVPT VGSSFVGMSL
SE_Spo VVTSSKKSES PVEYKAPLTI VCDGCFSKFR
KAFIDHPI.Q VTDHFLGLIL
Consensus VQYK-K--G- --E--APLTV VCDG-FSKFR
KSL----V-- V-S-FVG-I-
SE_Ath KNCQLEEPEK LKLIM.SKPS FTMLYQISST
DVRCVFEVLP NNIPSISNGE
SE_Bna KNCQLEDPEK LKLIM.SKPS FTMLYQISST
DVRCVMEIFP GNIPSISNGE
SE_Pgi ENIDLPHINH GHVIL.ADPS PILFYKISST
EIRCLVDVPG QKVPCISNGE
SE_mus KDAPQFKPNF AELVL.VNPS PVLIYQISSS
ETRVL.VDIR GELP....RN
SE_rat KDAPQFKANF AELVL.VDPS PVLIYQISPS
ETRVL.VDIR GELP....RN
SE_hum KNAPQFKANH AELIL.ANPS PVLIYQISSS
ETRVL.VDIR GEMP....RN
SE_Cal KNAELPAKGK GHVLLGG.HA PALIYSVSPT
ETRVLCVYVS SKPPSAANDA
SE_Sce FNAKNPAPMH GHVILGSDHM PILVYQISPE
ETRILCAYNS PKVPA....D
SE_Spo TNPDYIAPGR GHVILSKVAP MVL.YPISST
EARILINYPG KNLPP..MET
Consensus KNA----P-- --LIL---PS PVLIYQISST ETR-L----- ---P------
SE_Ath MATFVKNTIA PQVPLKLRKI FLKGIDEGEH
IKAMPTKKMT ATLS...EKK
SE_Bna MAVYLKNTMA PQVPPELRKI FLKGIDEGAQ
IKAMPTKRME ATLS...EKQ
SE_Pgi LANYLKTVVA PQVPKQLYNS FIAAVDKG.N
IRTMPNRSMP ADPH...PTP
SE_mus LREYMAEQIY PQLPEHLKES FLEASQNG.R
LRTMPASFLP ...PSSVNKR
SE_rat LREYMTEQIY PQIPDHLKES FLEACQNA.R
LRTMPASFLP ...PSSVNKR
SE_hum LREYMVEKIY PQIPDHLKEP FLEATDNS.H
LRSMPASFLP ...PSSVKKR
SE_Cal VYKYLRDNIL PAIPKETVPA FKEALEER.K
FRIMPNQYLS AMKQGSENHK
SE_Sce IKSWMIKDVQ PFIPKSLRPS FDEAVSQG.K
FRAMPNSYLP ...ARQNDVT
SE_Spo LKKYVLESCV PNMPEKL.RP SLKAAVYNDR
LRSMPNQFLP ...PTVNRTK
Consensus L--Y----I- PQ-P--L--- FLEA---G--
-R-MP--FLP A-------K-
SE_Ath GVILLGDAFN
MRHPAIASGM MVLLSDILIL RRLLQP..LS
NLGNAQKISQ
SE_Bna GVIVLGDAFN
MRHPAIASGM MVVLSDILIL RRLLQP..LR
NLSDANKVSE
SE_Pgi GALLLGDAFN
MRHPLTGGGM TVALSDIVLI RDLLRP..LR
DLHDSSTLCK
SE_mus GVLILGDAYN
LRHPLTGGGM TVALKDIKLW RQLL..KDIP
DLYDDAAIFQ
SE_rat GVLLLGDAYN
LRHPLTGGGM TVALKDIKIW RQLL..KDIP
DLYDDAAIFQ
SE_hum GVLLLGDAYN
MRHPLTGGGM TVAFKDIKLW RKLL..KGIP
DLYDDAAIFE
SE_Cal GFILLGDSLN
MRHPLTGGGM TVGLNDSVLL AKLLHPKFVE
DFDDHQLIAK
SE_Sce GMCVIGDALN
MRHPLTGGGM TVGLHDVVLL IKKIGDL...
DFSDREKVLD
SE-Spo
GMILVGDSNN
MRHPLTGGGM TVCFHDAYLL SRFISPSAVP DLLDYERILN
Consensus GV-LLGDA-N
MRHPLTGGGM TV-L-DI-LL R-LL-P---- DL-D---I--
SE_Ath VIKSFYDIRK PM.SATVNTL GNAFSQVLVA
STDEAKEAMR QGCYDYLSSG
SE_Bna VIKSFYVIRK PM.SATVNTL GNAFSQVLIA
STDEAKEAMR QGCFDYLSSG
SE_Pgi YLESFYTLRK PV.ASTINTL AGALYKVFCA
SPDKARQEMR NACFDYLSLG
SE_mus AKKSFFWSRK RTHSFVVNVL AQALYELFSA
TDDSLHQ.LR KACFLYFKLG
SE_rat AKKSFFWSRK RSHSFVVNVL AQALYELFSA
TDDSLRQ.LR KACFLYFKLG
SE_hum AKKSFYWARK TSHSFVVNIL AQALYELFSA
TDDSLHQ.LR KACFLYFKLG
SE_Cal RLKTFHRKRK NLDA.VINTL SISLYSLFAA
DKKPLRI.LR NGCFKYFQRG
SE_Sce ELLDYHFERK SYDS.VINVL SVALYSLFAA
DSDNLK.ALQ KGCFKYFQRG
SE_Spo
QMNKFHWKRK GYSF.VINVL SIALYKLFTP KNRYMK.ALE
SGCIDYFKRG
Consensus --KSF---RK ---S-VVN-L --ALY-LF-A
--D-L--ALR -GCF-YF--G
SE_Ath GFRTSGMMAL LGGMNPRPIS LIYHLCAITL
SSIGHLLSPF P...SPLRIW
SE_Bna GFRTSGMMAL LGGMNPRPLS LIFHLCGITL
SSIGQLLSPF P...SPLGIW
SE_Pgi GICSQGPIAL LSGLNPRPIS LFLHFFAVAI
YGVGRLLIPF P...SPKRMW
SE_mus GECVTGPVGL LSILSPHPLV LIRHFFSVAI
YATYFCFKSE PWATKPRALF
SE_rat GECLTGPVGL LSILSPDPLL LIRHFFSVAV
YATYFCFKSE PWATKPRALF
SE_hum GECVAGPVGL LSVLSPNPLV LIGHFFAVAI
YAVYFCFKSE PWITKPRALL
SE_Cal GECVNGPIGL LSGMLPFPML LFNHFFSVAF
YSVYLNFIER GLLGFPLALF
SE_Sce GDCVNKPVEF LSGVLPKPLQ LTRVFFAVAF
YTIYLNMEER GFLGLPMALL
SE_Spo
GNCVEGPIRL LGGLDHSPSH LIGHFYAVCL YGIYQYVLSG
PALLMPVRII
Consensus G-CV-GP--L LSGL-P-PL- LI-HFFAVA-
Y--Y------ P----P-AL-
SE_Ath HSLRLFGLAM KMLVPHLKAE GVSQMLFPVN
AAAYSKSYMA ATAL
SE_Bna HSLRLFG... ........AE GVSQMLSPAY
AAAYRKSYMT ATAL
SE_Pgi LGARLILGAS GIIFPIIKSE GLRQMFFPAI
VPAYYRAPPI H~~~
SE_mus SSGAVLYKAC SILFPLIYSE MKYLVH~~~~
~~~~~~~~~~ ~~~~
SE_rat SSGAILYKAC SIIFPLIYSE MKYLVH~~~~
~~~~~~~~~~ ~~~~
SE_hum SSGAVLYKAC SVIFPLIYSE MKYMVH~~~~
~~~~~~~~~~ ~~~~
SE_Cal EAFEVLFTAI VIFTPYLWNE IVR~~~~~~~
~~~~~~~~~~ ~~~~
SE_Sce EGIMILITAI RVFTPFLFGE LIG~~~~~~~
~~~~~~~~~~ ~~~~
SE_Spo ESLLIFLQAS LVIIPYILSE MSS~~~~~~~
~~~~~~~~~~ ~~~~
Consensus -S---L--A- ----P-I-SE ----------
---------- ----
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Key
In the above alignment SE
stands for squalene monooxygenase (squalene epoxidase). SE-Ath, Arabidopsis
thaliana; SE-Bna, Brassica napus; SE-Pgi, Panax ginseng;
SE-mus, mouse; SE-rat, rat; SE-Hum, human; SE-Cal, Candida albicans; SE-Sce,
Saccharomyces cerevisiae; SE-Spo,
Schizosaccharomyces pombe. A consensus sequence, where a
majority of sequences match, is shown in red, and the key residues in each
FAD-binding domain, based on one or more known flavoprotein structures,
are also shown in red.
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Other
Flavoproteins Related to Squalene Monooxygenase
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PSI-BLAST
was used to search the protein databases for
sequences related to squalene monooxygenase. Shown below is a selected
list of sequences returned after 3 iterations of the initial search, with
the best matches at the top.
| Protein |
NCBI
entry |
Flavo-
protein |
Function |
| CTF2A,
Arabidopsis thaliana |
gi|4164574 |
? |
unknown |
| 3-(3-Hydroxyphenyl)propionate
hydroxylase, E. coli |
sp|P77397|MHPA_ECOLI |
? |
3-(3-hydroxyphenyl)propionic
acid degradation pathway |
| Aklavinone
C-11 hydroxylase, Streptomyces peucetius |
gi|836907 |
? |
daunorubicin
biosynthesis, NADPH-dependent |
| Tetracycline
6-hydroxylase - Streptomyces aureofaciens |
pir||JC4098 |
? |
chlorination
of tetracycline |
| VISC
PROTEIN, E. coli |
sp|P25535|VISC_ECOLI |
? |
ubiquinone
biosynthesis? |
| kynurenine
3-monooxygenase, Drosophila melanogaster |
gi|1336011 |
? |
essential
for brown eye pigment synthesis |
| rifampin
monooxygenase, Rhodococcus equi |
gi|1785985 |
? |
Rifampin
antibiotic degradation |
| p-Hydroxybenzoate
hydroxylase, Pseudomonas fluorescens |
g230246 |
yes |
p-hydroxybenzoate
degradation; FAD monooxygenase |
| Zeaxanthin
epoxidase, Nicotiana plumbaginifolia |
sp|Q40412|ABA2_NICPL |
? |
abscisic
acid biosynthesis |
| 2,4-Dichlorophenol
6-monooxygenase, Ralstonia eutropha |
sp|P27138|TFDB_ALCEU |
yes |
Aromatic
hydrocarbon catabolism |
| pentachlorophenol
4-monooxygenase, Sphingomonas species UG30 |
gb|AAC15879.1| |
? |
p-nitrophenol
degradation |
| phenol
2-monooxygenase, Pseudomonas sp. EST1001 |
gi|145130 |
yes |
Aromatic
hydrocarbon catabolism |
| salicylate
hydroxylase, Pseudomonas putida |
sp|P23262|NHG1_PSEPU |
yes |
naphthalene
degradation |
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Comparison
of Squalene Monooxygenase to p-Hydroxybenzoate Hydroxylase |
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p-Hydroxybenzoate
hydroxylase (pHBH) is the prototype for FAD monooxygenases.
Its 3-dimensional structure was first determined in 1979 (Wierenga
et al., J. Mol. Biol. 131,55-73) and its amino acid
sequence in 1983 (Hofsteenge
et al., Eur. J. Biochem. 133, 91-108). An alignment
of squalene monooxygenase (SE) and pHBH is shown below; the two
proteins share 24% sequence identity over 394 amino acids.
Many amino acids involved in FAD binding in pHBH are conserved in
SE, suggesting similar overall structure. Both enzymes require
a source of reducing equivalents for monooxygenation; pHBH binds
NADPH directly, whereas SE uses cytochrome P450 reductase as a
source of electrons. Interestingly, pHBH lacks the typical
NADPH binding domain found in most enzymes that utilize this
cofactor, and is thought instead to bind NADPH at the interface that
forms between paired identical molecules (the "dimer
interface"; Eppink
et al., J. Biol. Chem. 273, 21031-9, 1998).
The
SE sequence is shown above the pHBH sequence; note that the SE
sequence is 180 amino acids longer than pHBH, with the similarity
beginning just before the FAD pyrophosphate binding segment (GxGxxG)
noted above in the earlier alignment. Vertical lines (|)
indicate identity; colons (:)
close similarity; periods (.)
lesser similarity. The FAD binding segments similarly
identified above are highlighted.
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101 GTNISETSLIGTAACTSTSSQNDPEVIIVGAGVLGSALAAVLSRDGRKVT
150
:| |:||| | | .| : |
1 .....................MKTQVAIIGAGPSGLLLGQLLHKAGIDNV
29
151 VIERDLKEPDRIVGEF....LQPGGYHVLKDLGLGDTVEGLDAQVVNGYM
196
::|| . ||
:.| |: | .|:: |.
| | | |
30 ILER..QTPDYVLGRIRAGVLEQGMVDLLREAGV.DRRMARDGLVHEGVE
76
197 IHDQESKSEVQIPYPLSENNQVQSGRAFHHGRFIMSLRKAAMAEPNAKFI
246
| : :
: ||
| | :|
|.| | .
77 IAFAGQRRRIDLK.RLSGGKTVTVYGQTEVTRDLMEAREACGATTVYQAA
125
247 EGVVLQLLEEDDVVMGVQYKDKETGDIKELHAPLTVVADGLFSKFRKSLV
296
| | | |: : . :
:| |:
|
|| |.|:
126 E.VRLHDLQGERPYVTFE.RD...GERLRLDCDYIAGCDGFHGISRQSIP 170
297 SNKVSVSSHF..VGFLMKNAPQFKANHAELILAN.PSP.VLIYQISSSET
342
. :. |
|.| | .| ||| ||
| | | |.. .
171 AERLKVFERVYPFGWLGLLADTPPVSH.ELIYANHPRGFALCSQRSATRS
219
343 RVLVDIRGEMPRNLREYMVEKIYPQIPDHLKEPFLE..ATDNSHLRSM.P
389
| | : : .
:: |: : :: | |
| | :|. |
220 RYYVQV..PLTEKVEDWSDERFWTELKARLPAEVAEKLVTGPSLEKSIAP
267
390 ASFLPPSSVKKRGVLLLGDAYNMRHPLTGGGMTVAFKDIK.LWRKLLK..
436
.. . | ||| .. | |: .|
|: |:| |||
268 LRSFVVEPMQHGRLFLAGDAAHIVPPTGAKGLNLAASDVSTLYRLLLKAY
317
437 ..GIPDLYDDAAIFEAKKSFYWARKTSHSFVVNILAQALYELFSATDDSL
484
| :| : .
:: | . .. .:|
. | ||
318 REGRGELLERYSAICLRR..IWKAERFSWWMTSVLHR.....FPDTDAFS
360
485 HQLRKACFLYFKLGGECVAGPVGLLSVLSPNPLVLIGHFFAVAIYAVYFC
534
.:.. |: ||
| : | |
:
361 QRIQQTELEYY.LGSEAGLATIAENYVGLPYEEIE...............
394
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| The
3-Dimensional Structure of p-Hydroxybenzoate Hydroxylase |
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The pHBH molecule is shown
below; squalene monooxygenase presumably adopts a similar overall
structure. In this figure the FAD group is shown in yellow,
and the p-hydroxybenzoate substrate is in magenta.
Click
here to go to a 3-D interactive CHIME image of the pHBH
dimer at Wageningen Agricultural University; hold the left mouse
button down to rotate the molecule and right click on the image for
a menu of display options (I recommend 'display-backbone',
'select-hetero-ligand' followed by 'display-sticks' and
'select-change color to-yellow'). Other sources to view this
molecule: the Protein
Explorer at the University of Massachusetts and NCBI
Structure, using the CN3D viewer (the PDB/MMDB Id is '1PHH').
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Additional sources of
information on pHBH can be found at:
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More information on
squalene monooxygenase:
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Back
to Squalene Monooxygenase Page
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Comments to
Todd D. Porter,
Pharmaceutical Sciences, University of Kentucky College of Pharmacy,
Lexington, KY 40536-0082. Phone 859 257-1137; FAX 859 257-7564
Last Modified: December 02, 2001
Copyright © 2000, University of Kentucky Chandler Medical Center
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