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P05979

- PGH1_SHEEP

UniProt

P05979 - PGH1_SHEEP

Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

Organism
Ovis aries (Sheep)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 2 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.1 Publication

    Catalytic activityi

    Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

    Cofactori

    Binds 1 heme B (iron-protoporphyrin IX) group per subunit.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei104 – 1041Not glycosylated
    Active sitei207 – 2071Proton acceptor
    Active sitei385 – 3851For cyclooxygenase activity1 Publication
    Metal bindingi388 – 3881Iron (heme axial ligand)
    Sitei530 – 5301Aspirin-acetylated serine

    GO - Molecular functioni

    1. dioxygenase activity Source: UniProtKB-KW
    2. heme binding Source: InterPro
    3. metal ion binding Source: UniProtKB-KW
    4. peroxidase activity Source: UniProtKB-KW
    5. prostaglandin-endoperoxide synthase activity Source: UniProtKB-EC

    GO - Biological processi

    1. prostaglandin biosynthetic process Source: UniProtKB
    2. regulation of blood pressure Source: UniProtKB
    3. response to oxidative stress Source: InterPro

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BRENDAi1.14.99.1. 4472.
    SABIO-RKP05979.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei4121. OarPGHS01.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin G/H synthase 1 (EC:1.14.99.1)
    Alternative name(s):
    Cyclooxygenase-1
    Short name:
    COX-1
    Prostaglandin H2 synthase 1
    Short name:
    PGH synthase 1
    Short name:
    PGHS-1
    Short name:
    PHS 1
    Prostaglandin-endoperoxide synthase 1
    Gene namesi
    Name:PTGS1
    Synonyms:COX1
    OrganismiOvis aries (Sheep)
    Taxonomic identifieri9940 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
    ProteomesiUP000002356: Unplaced

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW
    4. intracellular membrane-bounded organelle Source: UniProtKB
    5. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi385 – 3851Y → F: Abolishes cyclooxygenase activity.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Add
    BLAST
    Chaini25 – 600576Prostaglandin G/H synthase 1PRO_0000023871Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi36 ↔ 47
    Disulfide bondi37 ↔ 159
    Disulfide bondi41 ↔ 57
    Disulfide bondi59 ↔ 69
    Glycosylationi68 – 681N-linked (GlcNAc...)1 Publication
    Glycosylationi144 – 1441N-linked (GlcNAc...)1 Publication
    Glycosylationi410 – 4101N-linked (GlcNAc...)1 Publication
    Disulfide bondi569 ↔ 575

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homodimer.

    Structurei

    Secondary structure

    1
    600
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi35 – 384
    Beta strandi46 – 505
    Turni51 – 533
    Beta strandi54 – 585
    Beta strandi62 – 654
    Turni66 – 694
    Helixi74 – 829
    Helixi86 – 938
    Helixi97 – 1037
    Helixi108 – 12114
    Beta strandi130 – 1334
    Beta strandi134 – 1363
    Helixi139 – 1435
    Beta strandi149 – 1524
    Beta strandi159 – 1613
    Beta strandi164 – 1674
    Helixi174 – 1818
    Helixi196 – 20611
    Turni207 – 2093
    Turni214 – 2163
    Beta strandi220 – 2223
    Beta strandi227 – 2293
    Helixi231 – 2344
    Helixi238 – 2447
    Beta strandi255 – 2573
    Beta strandi260 – 2623
    Turni266 – 2683
    Helixi281 – 2833
    Beta strandi288 – 2914
    Helixi292 – 2943
    Helixi296 – 31924
    Helixi325 – 34622
    Helixi348 – 3536
    Helixi363 – 3664
    Beta strandi367 – 3693
    Helixi379 – 3846
    Helixi388 – 3903
    Beta strandi393 – 3975
    Beta strandi400 – 4023
    Helixi404 – 4074
    Helixi413 – 4175
    Helixi419 – 42810
    Beta strandi434 – 4385
    Turni442 – 4443
    Helixi445 – 45713
    Helixi463 – 4697
    Helixi478 – 4825
    Beta strandi483 – 4853
    Helixi486 – 49510
    Helixi498 – 5003
    Helixi503 – 5097
    Beta strandi517 – 5193
    Helixi520 – 53516
    Helixi538 – 5403
    Turni542 – 5443
    Helixi547 – 5504
    Helixi553 – 5608
    Helixi564 – 5696
    Beta strandi572 – 5743

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CQEX-ray3.10A/B21-600[»]
    1DIYX-ray3.00A32-584[»]
    1DJJmodel-A25-600[»]
    1EBVX-ray3.20A33-583[»]
    1EQGX-ray2.61A/B21-600[»]
    1EQHX-ray2.70A/B21-600[»]
    1FE2X-ray3.00A25-600[»]
    1HT5X-ray2.75A/B33-583[»]
    1HT8X-ray2.69A/B33-583[»]
    1IGXX-ray3.10A25-600[»]
    1IGZX-ray2.90A25-600[»]
    1PGEX-ray3.50A/B25-600[»]
    1PGFX-ray4.50A/B25-600[»]
    1PGGX-ray4.50A/B25-600[»]
    1PRHX-ray3.50A/B33-586[»]
    1PTHX-ray3.40A/B25-600[»]
    1Q4GX-ray2.00A/B32-584[»]
    1U67X-ray3.10A1-600[»]
    2AYLX-ray2.00A/B32-584[»]
    2OYEX-ray2.85P1-600[»]
    2OYUX-ray2.70P1-600[»]
    3KK6X-ray2.75A/B32-584[»]
    3N8VX-ray3.05A/B32-584[»]
    3N8WX-ray2.75A/B32-584[»]
    3N8XX-ray2.75A/B32-584[»]
    3N8YX-ray2.60A/B32-584[»]
    3N8ZX-ray2.90A/B32-584[»]
    4O1ZX-ray2.40A/B32-600[»]
    ProteinModelPortaliP05979.
    SMRiP05979. Positions 32-584.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05979.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei74 – 829Helical
    Transmembranei86 – 927Helical
    Transmembranei97 – 1059Helical
    Transmembranei108 – 12215HelicalAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini32 – 7039EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the prostaglandin G/H synthase family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOVERGENiHBG000366.

    Family and domain databases

    Gene3Di1.10.640.10. 1 hit.
    InterProiIPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view]
    PANTHERiPTHR11903:SF6. PTHR11903:SF6. 1 hit.
    PfamiPF03098. An_peroxidase. 1 hit.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    SUPFAMiSSF48113. SSF48113. 1 hit.
    PROSITEiPS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P05979-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRQSISLRF PLLLLLLSPS PVFSADPGAP APVNPCCYYP CQHQGICVRF    50
    GLDRYQCDCT RTGYSGPNCT IPEIWTWLRT TLRPSPSFIH FMLTHGRWLW 100
    DFVNATFIRD TLMRLVLTVR SNLIPSPPTY NIAHDYISWE SFSNVSYYTR 150
    ILPSVPRDCP TPMGTKGKKQ LPDAEFLSRR FLLRRKFIPD PQGTNLMFAF 200
    FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER QYQLRLFKDG 250
    KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLML 300
    YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ 350
    QLSGYFLQLK FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ 400
    DYSYEQFLFN TSMLVDYGVE ALVDAFSRQP AGRIGGGRNI DHHILHVAVD 450
    VIKESRVLRL QPFNEYRKRF GMKPYTSFQE LTGEKEMAAE LEELYGDIDA 500
    LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC SPEYWKASTF 550
    GGEVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPRQEDR PGVERPPTEL 600
    Length:600
    Mass (Da):68,791
    Last modified:June 1, 1994 - v2
    Checksum:i1B76E659BBA4353A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1 – 33MSR → MV in AAA31511. (PubMed:2831188)Curated
    Sequence conflicti5 – 51S → G AA sequence (PubMed:3129310)Curated
    Sequence conflicti63 – 9028GYSGP…PSFIH → AIPAPTAPSRRYGPGSGRLC GPAPLSST in AAA31576. (PubMed:3125548)CuratedAdd
    BLAST
    Sequence conflicti92 – 921M → L in CAA68719. (PubMed:3129310)Curated
    Sequence conflicti92 – 921M → L in AAA31511. (PubMed:2831188)Curated
    Sequence conflicti193 – 1931G → S in CAA68719. (PubMed:3129310)Curated
    Sequence conflicti540 – 5401C → E AA sequence (PubMed:6414516)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti97 – 971R → H.
    Natural varianti164 – 1641G → D.
    Natural varianti456 – 4561R → Q.
    Natural varianti520 – 5201E → K.
    Natural varianti520 – 5201E → Q.
    Natural varianti525 – 5251M → I.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03599 mRNA. Translation: AAA31576.1.
    Y00750 mRNA. Translation: CAA68719.1.
    M18243 mRNA. Translation: AAA31511.1.
    PIRiA28960.
    A29947.
    S00561.
    RefSeqiNP_001009476.1. NM_001009476.1.
    UniGeneiOar.445.

    Genome annotation databases

    GeneIDi443551.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03599 mRNA. Translation: AAA31576.1 .
    Y00750 mRNA. Translation: CAA68719.1 .
    M18243 mRNA. Translation: AAA31511.1 .
    PIRi A28960.
    A29947.
    S00561.
    RefSeqi NP_001009476.1. NM_001009476.1.
    UniGenei Oar.445.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CQE X-ray 3.10 A/B 21-600 [» ]
    1DIY X-ray 3.00 A 32-584 [» ]
    1DJJ model - A 25-600 [» ]
    1EBV X-ray 3.20 A 33-583 [» ]
    1EQG X-ray 2.61 A/B 21-600 [» ]
    1EQH X-ray 2.70 A/B 21-600 [» ]
    1FE2 X-ray 3.00 A 25-600 [» ]
    1HT5 X-ray 2.75 A/B 33-583 [» ]
    1HT8 X-ray 2.69 A/B 33-583 [» ]
    1IGX X-ray 3.10 A 25-600 [» ]
    1IGZ X-ray 2.90 A 25-600 [» ]
    1PGE X-ray 3.50 A/B 25-600 [» ]
    1PGF X-ray 4.50 A/B 25-600 [» ]
    1PGG X-ray 4.50 A/B 25-600 [» ]
    1PRH X-ray 3.50 A/B 33-586 [» ]
    1PTH X-ray 3.40 A/B 25-600 [» ]
    1Q4G X-ray 2.00 A/B 32-584 [» ]
    1U67 X-ray 3.10 A 1-600 [» ]
    2AYL X-ray 2.00 A/B 32-584 [» ]
    2OYE X-ray 2.85 P 1-600 [» ]
    2OYU X-ray 2.70 P 1-600 [» ]
    3KK6 X-ray 2.75 A/B 32-584 [» ]
    3N8V X-ray 3.05 A/B 32-584 [» ]
    3N8W X-ray 2.75 A/B 32-584 [» ]
    3N8X X-ray 2.75 A/B 32-584 [» ]
    3N8Y X-ray 2.60 A/B 32-584 [» ]
    3N8Z X-ray 2.90 A/B 32-584 [» ]
    4O1Z X-ray 2.40 A/B 32-600 [» ]
    ProteinModelPortali P05979.
    SMRi P05979. Positions 32-584.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P05979.
    ChEMBLi CHEMBL2949.

    Protein family/group databases

    PeroxiBasei 4121. OarPGHS01.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 443551.

    Organism-specific databases

    CTDi 5742.

    Phylogenomic databases

    HOVERGENi HBG000366.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    BRENDAi 1.14.99.1. 4472.
    SABIO-RK P05979.

    Miscellaneous databases

    EvolutionaryTracei P05979.

    Family and domain databases

    Gene3Di 1.10.640.10. 1 hit.
    InterProi IPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view ]
    PANTHERi PTHR11903:SF6. PTHR11903:SF6. 1 hit.
    Pfami PF03098. An_peroxidase. 1 hit.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48113. SSF48113. 1 hit.
    PROSITEi PS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence."
      Dewitt D.L., Smith W.L.
      Proc. Natl. Acad. Sci. U.S.A. 85:1412-1416(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Seminal vesicle.
    2. "Primary structure of sheep prostaglandin endoperoxide synthase deduced from cDNA sequence."
      Yokoyama C., Takai T., Tanabe T.
      FEBS Lett. 231:347-351(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    3. "Isolation and characterization of the complementary DNA for sheep seminal vesicle prostaglandin endoperoxide synthase (cyclooxygenase)."
      Merlie J., Fagan D., Mudd J., Needleman P.
      J. Biol. Chem. 263:3550-3553(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Isolation and covalent structure of the aspirin-modified, active-site region of prostaglandin synthetase."
      Roth G.J., Machuga E.T., Ozols J.
      Biochemistry 22:4672-4675(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 523-544.
    5. "The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases."
      Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F., Armstrong R.L., Smith W.L.
      J. Biol. Chem. 265:5192-5198(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: HEME-BINDING SITE.
    6. "Tyrosine 385 of prostaglandin endoperoxide synthase is required for cyclooxygenase catalysis."
      Shimokawa T., Kulmacz R.J., Dewitt D.L., Smith W.L.
      J. Biol. Chem. 265:20073-20076(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE TYR-385.
    7. "N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum."
      Otto J.C., Dewitt D.L., Smith W.L.
      J. Biol. Chem. 268:18234-18242(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-68; ASN-144 AND ASN-410, ABSENCE OF GLYCOSYLATION AT ASN-104.
    8. "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition."
      Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.
      J. Biol. Chem. 274:22903-22906(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AND INHIBITION BY NSAIDS.
    9. "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1."
      Picot D., Loll P.J., Garavito R.M.
      Nature 367:243-249(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
    10. "The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase."
      Loll P.J., Picot D., Garavito R.M.
      Nat. Struct. Biol. 2:637-643(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
    11. "Synthesis and use of iodinated antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site."
      Loll P.J., Picot D., Ekabo O., Garavito R.M.
      Biochemistry 35:7330-7340(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
    12. "The productive conformation of arachidonic acid bound to prostaglandin synthase."
      Malkowski M.G., Ginell S.L., Smith W.L., Garavito R.M.
      Science 289:1933-1937(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
    13. "Mutational and X-ray crystallographic analysis of the interaction of dihomo-gamma-linolenic acid with prostaglandin endoperoxide H synthases."
      Thuresson E.D., Malkowski M.G., Lakkides K.M., Rieke C.J., Mulichak A.M., Ginell S.L., Garavito R.M., Smith W.L.
      J. Biol. Chem. 276:10358-10365(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
    14. "Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations."
      Selinsky B.S., Gupta K., Sharkey C.T., Loll P.J.
      Biochemistry 40:5172-5180(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS).

    Entry informationi

    Entry nameiPGH1_SHEEP
    AccessioniPrimary (citable) accession number: P05979
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 137 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.
    Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PGHS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PGHS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.
    PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3