ERYA2_SACER
ID ERYA2_SACER Reviewed; 3567 AA.
AC Q03132; Q54096;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=6-deoxyerythronolide-B synthase EryA2, modules 3 and 4 {ECO:0000305};
DE Short=DEBS 2 {ECO:0000303|PubMed:1740151};
DE EC=2.3.1.94 {ECO:0000269|PubMed:21095573};
DE AltName: Full=6-deoxyerythronolide B synthase II {ECO:0000303|PubMed:1740151};
DE AltName: Full=Erythronolide synthase;
DE AltName: Full=ORF B {ECO:0000303|PubMed:1740151};
GN Name=eryA {ECO:0000303|PubMed:1740151};
OS Saccharopolyspora erythraea (Streptomyces erythraeus).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Saccharopolyspora.
OX NCBI_TaxID=1836;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBUNIT.
RX PubMed=2024119; DOI=10.1126/science.2024119;
RA Donadio S., Staver M.J., McAlpine J.B., Swanson S.J., Katz L.;
RT "Modular organization of genes required for complex polyketide
RT biosynthesis.";
RL Science 252:675-679(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBUNIT.
RC STRAIN=ATCC 11635 / DSM 40517 / IFO 13426 / JCM 4026 / NCIB 8594;
RX PubMed=1740151; DOI=10.1111/j.1432-1033.1992.tb16603.x;
RA Bevitt D.J., Cortes J., Haydock S.F., Leadlay P.F.;
RT "6-deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea.
RT Cloning of the structural gene, sequence analysis and inferred domain
RT structure of the multifunctional enzyme.";
RL Eur. J. Biochem. 204:39-49(1992).
RN [3]
RP PROTEIN SEQUENCE OF 2-12.
RC STRAIN=CA340;
RX PubMed=1618327; DOI=10.1016/0014-5793(92)80624-p;
RA Caffrey P., Bevitt D.J., Staunton J., Leadlay P.F.;
RT "Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides
RT of the erythromycin-producing polyketide synthase from Saccharopolyspora
RT erythraea.";
RL FEBS Lett. 304:225-228(1992).
RN [4]
RP FUNCTION, PATHWAY, AND SUBUNIT.
RX PubMed=17328673; DOI=10.1146/annurev.biochem.76.053105.093515;
RA Khosla C., Tang Y., Chen A.Y., Schnarr N.A., Cane D.E.;
RT "Structure and mechanism of the 6-deoxyerythronolide B synthase.";
RL Annu. Rev. Biochem. 76:195-221(2007).
RN [5]
RP FUNCTION, MUTAGENESIS OF TYR-2874, AND ACTIVE SITE.
RX PubMed=19022183; DOI=10.1016/j.chembiol.2008.09.012;
RA Kwan D.H., Sun Y., Schulz F., Hong H., Popovic B., Sim-Stark J.C.,
RA Haydock S.F., Leadlay P.F.;
RT "Prediction and manipulation of the stereochemistry of enoylreduction in
RT modular polyketide synthases.";
RL Chem. Biol. 15:1231-1240(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21095573; DOI=10.1016/j.chembiol.2010.09.013;
RA Zhang H., Wang Y., Wu J., Skalina K., Pfeifer B.A.;
RT "Complete biosynthesis of erythromycin A and designed analogs using E. coli
RT as a heterologous host.";
RL Chem. Biol. 17:1232-1240(2010).
RN [7]
RP FUNCTION, MUTAGENESIS OF SER-1254 AND TYR-1267, DISRUPTION PHENOTYPE,
RP REACTION MECHANISM, AND ACTIVE SITE.
RX PubMed=21570406; DOI=10.1016/j.jmb.2011.04.065;
RA Zheng J., Keatinge-Clay A.T.;
RT "Structural and functional analysis of C2-type ketoreductases from modular
RT polyketide synthases.";
RL J. Mol. Biol. 410:105-117(2011).
RN [8]
RP STRUCTURE BY NMR OF 3488-3547, AND SUBUNIT.
RX PubMed=12954331; DOI=10.1016/s1074-5521(03)00156-x;
RA Broadhurst R.W., Nietlispach D., Wheatcroft M.P., Leadlay P.F.,
RA Weissman K.J.;
RT "The structure of docking domains in modular polyketide synthases.";
RL Chem. Biol. 10:723-731(2003).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 27-922 IN COMPLEX WITH SUBSTRATE
RP ANALOG, FUNCTION, SUBSTRATE SPECIFICITY, ACTIVE SITE, COFACTOR, AND
RP SUBUNIT.
RX PubMed=17719492; DOI=10.1016/j.chembiol.2007.07.012;
RA Tang Y., Chen A.Y., Kim C.Y., Cane D.E., Khosla C.;
RT "Structural and mechanistic analysis of protein interactions in module 3 of
RT the 6-deoxyerythronolide B synthase.";
RL Chem. Biol. 14:931-943(2007).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 2362-2653, FUNCTION, MUTAGENESIS
RP OF ARG-2640, SUBUNIT, AND ACTIVE SITE.
RX PubMed=18952099; DOI=10.1016/j.jmb.2008.09.084;
RA Keatinge-Clay A.;
RT "Crystal structure of the erythromycin polyketide synthase dehydratase.";
RL J. Mol. Biol. 384:941-953(2008).
CC -!- FUNCTION: Involved in the biosynthesis of antibiotic erythromycin via
CC the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6-
CC dEB). {ECO:0000269|PubMed:17719492, ECO:0000269|PubMed:18952099,
CC ECO:0000269|PubMed:21095573, ECO:0000269|PubMed:21570406,
CC ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:19022183}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 (S)-methylmalonyl-CoA + 12 H(+) + 6 NADPH + propanoyl-CoA =
CC 6-deoxyerythronolide B + 6 CO2 + 7 CoA + H2O + 6 NADP(+);
CC Xref=Rhea:RHEA:23068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16089, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.94;
CC Evidence={ECO:0000269|PubMed:21095573};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:17719492};
CC Note=Binds 2 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis; erythromycin biosynthesis.
CC {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21095573}.
CC -!- SUBUNIT: Homodimer (PubMed:12954331, PubMed:17719492, PubMed:18952099).
CC Erythronolide synthase is composed of EryAI, EryAII and EryAIII
CC multimodular (2 modules) polypeptides each coding for a functional
CC synthase subunit which participates in 2 of the six FAS-like elongation
CC steps required for formation of the polyketide. Module 1, 2, 3, 4, 5,
CC and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6,
CC respectively. {ECO:0000269|PubMed:12954331,
CC ECO:0000269|PubMed:17719492, ECO:0000269|PubMed:18952099,
CC ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:1740151,
CC ECO:0000305|PubMed:2024119}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to produce 6-
CC deoxyerythronolide (6-dEB), however a tetraketide lactone shunt is
CC produced. {ECO:0000269|PubMed:21570406}.
CC -!- MISCELLANEOUS: Type I modular polyketide synthases (PKSs) catalyze the
CC step-wise condensation of simple carboxylic acid derivatives.
CC Organizationally, type I PKSs are arranged into modules, wherein each
CC module is comprised of a set of catalytic activities that is
CC responsible for a single elongation of the polyketide chain and the
CC appropriate reductive processing of the beta-keto functionality. A
CC minimal elongation module contains an acyl transferase (AT) domain, an
CC acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The
CC AT domain is responsible for loading the methylmalonyl-CoA extender
CC unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS
CC domain decarboxylates and then condenses the ACP-bound extender unit
CC with the growing polyketide chain obtained from the preceding module to
CC yield an ACP-bound beta-ketoacyl intermediate. In addition to the three
CC core domains, each elongation module may contain up to three additional
CC domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase
CC (ER) that are responsible for the reductive processing of the beta-keto
CC functionality prior to the next extension step. The presence of a KR
CC domain alone gives rise to a beta-hydroxyl functionality, the presence
CC of both a KR and a DH domain generates an alkene, while the combination
CC of KR, DH, and ER results in complete reduction to the alkane. Finally,
CC a thioesterase (TE) domain, typically found at the terminus of the last
CC elongation module, catalyzes the termination of polyketide
CC biosynthesis. The activity of this domain results in cleavage of the
CC acyl chain from the adjacent ACP and formation of the macrocyclic ring.
CC {ECO:0000305|PubMed:17328673, ECO:0000305|PubMed:21570406}.
CC -!- MISCELLANEOUS: C2-type beta-ketoacyl reductase 1 is unable to bind NADP
CC and seems to act as a racemase. {ECO:0000269|PubMed:21570406}.
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DR EMBL; M63677; AAA26494.1; -; Genomic_DNA.
DR EMBL; X62569; CAA44448.1; -; Genomic_DNA.
DR PIR; S23070; S23070.
DR PDB; 1PZQ; NMR; -; A/B=3490-3547.
DR PDB; 1PZR; NMR; -; A/B=3548-3567.
DR PDB; 2QO3; X-ray; 2.59 A; A/B=27-922.
DR PDB; 3EL6; X-ray; 1.85 A; A=2362-2653.
DR PDB; 6C9U; X-ray; 2.09 A; A=2-922.
DR PDB; 7M7E; EM; 3.20 A; A/B=2-922.
DR PDB; 7S6C; EM; 3.10 A; A/B/C/D=2-30.
DR PDB; 7S6D; EM; 3.10 A; A/B/C=2-30.
DR PDBsum; 1PZQ; -.
DR PDBsum; 1PZR; -.
DR PDBsum; 2QO3; -.
DR PDBsum; 3EL6; -.
DR PDBsum; 6C9U; -.
DR PDBsum; 7M7E; -.
DR PDBsum; 7S6C; -.
DR PDBsum; 7S6D; -.
DR BMRB; Q03132; -.
DR SMR; Q03132; -.
DR ABCD; Q03132; 1 sequenced antibody.
DR BioCyc; MetaCyc:MON-17078; -.
DR BRENDA; 2.3.1.94; 5518.
DR BRENDA; 2.3.1.B32; 5518.
DR UniPathway; UPA00240; -.
DR EvolutionaryTrace; Q03132; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0047879; F:erythronolide synthase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; TAS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0033068; P:macrolide biosynthetic process; IMP:UniProtKB.
DR DisProt; DP01272; -.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR036347; DEBS_docking_sf.
DR InterPro; IPR015357; Erythronolide_synth_docking.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR015083; Polyketide_synth_docking.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 2.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF08990; Docking; 1.
DR Pfam; PF09277; Erythro-docking; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 2.
DR Pfam; PF00109; ketoacyl-synt; 2.
DR Pfam; PF02801; Ketoacyl-synt_C; 2.
DR Pfam; PF08659; KR; 2.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 2.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF101166; SSF101166; 1.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 5.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF55048; SSF55048; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Antibiotic biosynthesis;
KW Direct protein sequencing; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1618327"
FT CHAIN 2..3567
FT /note="6-deoxyerythronolide-B synthase EryA2, modules 3 and
FT 4"
FT /id="PRO_0000180294"
FT DOMAIN 1395..1470
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3413..3488
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 33..1467
FT /note="Module 3"
FT /evidence="ECO:0000305"
FT REGION 33..458
FT /note="Beta-ketoacyl synthase 1"
FT /evidence="ECO:0000305"
FT REGION 560..880
FT /note="Acyltransferase 1"
FT /evidence="ECO:0000305"
FT REGION 1132..1297
FT /note="C2-type beta-ketoacyl reductase 1"
FT /evidence="ECO:0000305"
FT REGION 1364..1385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1491..3485
FT /note="Module 4"
FT /evidence="ECO:0000305"
FT REGION 1491..1915
FT /note="Beta-ketoacyl synthase 2"
FT /evidence="ECO:0000305"
FT REGION 2015..2331
FT /note="Acyltransferase 2"
FT /evidence="ECO:0000305"
FT REGION 2377..2645
FT /note="Dehydratase"
FT /evidence="ECO:0000305"
FT REGION 2831..3131
FT /note="Enoyl reductase"
FT /evidence="ECO:0000305"
FT REGION 3141..3317
FT /note="Beta-ketoacyl reductase 2"
FT /evidence="ECO:0000305"
FT ACT_SITE 202
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 1 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022,
FT ECO:0000305|PubMed:17719492"
FT ACT_SITE 651
FT /note="Acyl-ester intermediate; for acyltransferase 1
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1267
FT /note="For C2-type beta-ketoacyl reductase 1 and probable
FT racemase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9ZGI4,
FT ECO:0000305|PubMed:21570406"
FT ACT_SITE 1661
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase 2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2105
FT /note="Acyl-ester intermediate; for acyltransferase 2
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2409
FT /note="Proton acceptor, for dehydratase activity"
FT /evidence="ECO:0000305|PubMed:18952099"
FT ACT_SITE 2571
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000305|PubMed:18952099"
FT ACT_SITE 2874
FT /note="For enoyl reductase activity"
FT /evidence="ECO:0000305|PubMed:19022183"
FT ACT_SITE 3287
FT /note="For beta-ketoacyl reductase 2 activity"
FT /evidence="ECO:0000305"
FT BINDING 2964..2973
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:19022183"
FT BINDING 3149..3152
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3173..3176
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3202..3203
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 3250
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03131"
FT BINDING 3272..3273
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT SITE 155
FT /note="Important for substrate specificity of the beta-
FT ketoacyl synthase 1"
FT /evidence="ECO:0000305|PubMed:17719492"
FT SITE 156
FT /note="Important for substrate specificity of the beta-
FT ketoacyl synthase 1"
FT /evidence="ECO:0000305|PubMed:17719492"
FT MOD_RES 1430
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3448
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1254
FT /note="S->F: Produces tetraketide lactone shunt and also 6-
FT deoxyerythronolide (6-dEB)."
FT /evidence="ECO:0000269|PubMed:21570406"
FT MUTAGEN 1267
FT /note="Y->F: Produces tetraketide lactone shunt and also 6-
FT deoxyerythronolide (6-dEB)."
FT /evidence="ECO:0000269|PubMed:21570406"
FT MUTAGEN 2640
FT /note="R->D: Decreased production of the erythromycin
FT precursor 6-deoxyerythronolide B (6-dEB)."
FT /evidence="ECO:0000269|PubMed:18952099"
FT MUTAGEN 2874
FT /note="Y->V: Switches the configuration of the C-2 methyl
FT group of the product."
FT /evidence="ECO:0000269|PubMed:19022183"
FT CONFLICT 438
FT /note="R -> A (in Ref. 2; CAA44448)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="T -> S (in Ref. 2; CAA44448)"
FT /evidence="ECO:0000305"
FT CONFLICT 1241
FT /note="L -> F (in Ref. 2; CAA44448)"
FT /evidence="ECO:0000305"
FT CONFLICT 2664
FT /note="G -> V (in Ref. 2; CAA44448)"
FT /evidence="ECO:0000305"
FT HELIX 3..30
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 33..42
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 49..58
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:7M7E"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 104..108
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 111..116
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 119..134
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 178..189
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 204..217
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 236..242
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:7M7E"
FT STRAND 268..276
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 289..298
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 310..323
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 344..354
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:2QO3"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:7M7E"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 382..396
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 418..421
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 436..442
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 446..455
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 472..480
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 481..495
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 502..511
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 517..526
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 527..538
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 547..551
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:7M7E"
FT STRAND 559..563
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 571..574
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 575..580
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 582..594
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 596..598
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 603..607
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 619..639
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 645..649
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 653..660
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 666..682
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 683..685
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 688..691
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 696..703
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:2QO3"
FT STRAND 717..719
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 721..725
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 727..738
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 740..742
FT /evidence="ECO:0007829|PDB:7M7E"
FT STRAND 745..747
FT /evidence="ECO:0007829|PDB:7M7E"
FT HELIX 756..761
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 762..769
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 778..783
FT /evidence="ECO:0007829|PDB:6C9U"
FT TURN 784..787
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 788..790
FT /evidence="ECO:0007829|PDB:2QO3"
FT HELIX 792..794
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 797..805
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 810..819
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 824..827
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 829..831
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 835..844
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 845..847
FT /evidence="ECO:0007829|PDB:6C9U"
FT STRAND 852..854
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 864..876
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 883..886
FT /evidence="ECO:0007829|PDB:6C9U"
FT HELIX 2368..2370
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2380..2385
FT /evidence="ECO:0007829|PDB:3EL6"
FT TURN 2387..2389
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2392..2398
FT /evidence="ECO:0007829|PDB:3EL6"
FT TURN 2400..2402
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2404..2408
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2409..2411
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2414..2416
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2419..2433
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2437..2443
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2454..2463
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2469..2477
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2482..2484
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2488..2496
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2522..2528
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2531..2533
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2535..2537
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2540..2546
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2549..2555
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2567..2575
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 2576..2579
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2590..2600
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2605..2613
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2618..2624
FT /evidence="ECO:0007829|PDB:3EL6"
FT STRAND 2630..2640
FT /evidence="ECO:0007829|PDB:3EL6"
FT HELIX 3498..3511
FT /evidence="ECO:0007829|PDB:1PZQ"
FT HELIX 3518..3536
FT /evidence="ECO:0007829|PDB:1PZQ"
FT HELIX 3550..3562
FT /evidence="ECO:0007829|PDB:1PZR"
SQ SEQUENCE 3567 AA; 374421 MW; EE6284F4738AA0C0 CRC64;
MTDSEKVAEY LRRATLDLRA ARQRIRELES DPIAIVSMAC RLPGGVNTPQ RLWELLREGG
ETLSGFPTDR GWDLARLHHP DPDNPGTSYV DKGGFLDDAA GFDAEFFGVS PREAAAMDPQ
QRLLLETSWE LVENAGIDPH SLRGTATGVF LGVAKFGYGE DTAAAEDVEG YSVTGVAPAV
ASGRISYTMG LEGPSISVDT ACSSSLVALH LAVESLRKGE SSMAVVGGAA VMATPGVFVD
FSRQRALAAD GRSKAFGAGA DGFGFSEGVT LVLLERLSEA RRNGHEVLAV VRGSALNQDG
ASNGLSAPSG PAQRRVIRQA LESCGLEPGD VDAVEAHGTG TALGDPIEAN ALLDTYGRDR
DADRPLWLGS VKSNIGHTQA AAGVTGLLKV VLALRNGELP ATLHVEEPTP HVDWSSGGVA
LLAGNQPWRR GERTRRARVS AFGISGTNAH VIVEEAPERE HRETTAHDGR PVPLVVSART
TAALRAQAAQ IAELLERPDA DLAGVGLGLA TTRARHEHRA AVVASTREEA VRGLREIAAG
AATADAVVEG VTEVDGRNVV FLFPGQGSQW AGMGAELLSS SPVFAGKIRA CDESMAPMQD
WKVSDVLRQA PGAPGLDRVD VVQPVLFAVM VSLAELWRSY GVEPAAVVGH SQGEIAAAHV
AGALTLEDAA KLVVGRSRLM RSLSGEGGMA AVALGEAAVR ERLRPWQDRL SVAAVNGPRS
VVVSGEPGAL RAFSEDCAAE GIRVRDIDVD YASHSPQIER VREELLETTG DIAPRPARVT
FHSTVESRSM DGTELDARYW YRNLRETVRF ADAVTRLAES GYDAFIEVSP HPVVVQAVEE
AVEEADGAED AVVVGSLHRD GGDLSAFLRS MATAHVSGVD IRWDVALPGA APFALPTYPF
QRKRYWLQPA APAAASDELA YRVSWTPIEK PESGNLDGDW LVVTPLISPE WTEMLCEAIN
ANGGRALRCE VDTSASRTEM AQAVAQAGTG FRGVLSLLSS DESACRPGVP AGAVGLLTLV
QALGDAGVDA PVWCLTQGAV RTPADDDLAR PAQTTAHGFA QVAGLELPGR WGGVVDLPES
VDDAALRLLV AVLRGGGRAE DHLAVRDGRL HGRRVVRASL PQSGSRSWTP HGTVLVTGAA
SPVGDQLVRW LADRGAERLV LAGACPGDDL LAAVEEAGAS AVVCAQDAAA LREALGDEPV
TALVHAGTLT NFGSISEVAP EEFAETIAAK TALLAVLDEV LGDRAVEREV YCSSVAGIWG
GAGMAAYAAG SAYLDALAEH HRARGRSCTS VAWTPWALPG GAVDDGYLRE RGLRSLSADR
AMRTWERVLA AGPVSVAVAD VDWPVLSEGF AATRPTALFA ELAGRGGQAE AEPDSGPTGE
PAQRLAGLSP DEQQENLLEL VANAVAEVLG HESAAEINVR RAFSELGLDS LNAMALRKRL
SASTGLRLPA SLVFDHPTVT ALAQHLRARL VGDADQAAVR VVGAADESEP IAIVGIGCRF
PGGIGSPEQL WRVLAEGANL TTGFPADRGW DIGRLYHPDP DNPGTSYVDK GGFLTDAADF
DPGFFGITPR EALAMDPQQR LMLETAWEAV ERAGIDPDAL RGTDTGVFVG MNGQSYMQLL
AGEAERVDGY QGLGNSASVL SGRIAYTFGW EGPALTVDTA CSSSLVGIHL AMQALRRGEC
SLALAGGVTV MSDPYTFVDF STQRGLASDG RCKAFSARAD GFALSEGVAA LVLEPLSRAR
ANGHQVLAVL RGSAVNQDGA SNGLAAPNGP SQERVIRQAL AASGVPAADV DVVEAHGTGT
ELGDPIEAGA LIATYGQDRD RPLRLGSVKT NIGHTQAAAG AAGVIKVVLA MRHGMLPRSL
HADELSPHID WESGAVEVLR EEVPWPAGER PRRAGVSSFG VSGTNAHVIV EEAPAEQEAA
RTERGPLPFV LSGRSEAVVA AQARALAEHL RDTPELGLTD AAWTLATGRA RFDVRAAVLG
DDRAGVCAEL DALAEGRPSA DAVAPVTSAP RKPVLVFPGQ GAQWVGMARD LLESSEVFAE
SMSRCAEALS PHTDWKLLDV VRGDGGPDPH ERVDVLQPVL FSIMVSLAEL WRAHGVTPAA
VVGHSQGEIA AAHVAGALSL EAAAKVVALR SQVLRELDDQ GGMVSVGASR DELETVLARW
DGRVAVAAVN GPGTSVVAGP TAELDEFFAE AEAREMKPRR IAVRYASHSP EVARIEDRLA
AELGTITAVR GSVPLHSTVT GEVIDTSAMD ASYWYRNLRR PVLFEQAVRG LVEQGFDTFV
EVSPHPVLLM AVEETAEHAG AEVTCVPTLR REQSGPHEFL RNLLRAHVHG VGADLRPAVA
GGRPAELPTY PFEHQRFWPR PHRPADVSAL GVRGAEHPLL LAAVDVPGHG GAVFTGRLST
DEQPWLAEHV VGGRTLVPGS VLVDLALAAG EDVGLPVLEE LVLQRPLVLA GAGALLRMSV
GAPDESGRRT IDVHAAEDVA DLADAQWSQH ATGTLAQGVA AGPRDTEQWP PEDAVRIPLD
DHYDGLAEQG YEYGPSFQAL RAAWRKDDSV YAEVSIAADE EGYAFHPVLL DAVAQTLSLG
ALGEPGGGKL PFAWNTVTLH ASGATSVRVV ATPAGADAMA LRVTDPAGHL VATVDSLVVR
STGEKWEQPE PRGGEGELHA LDWGRLAEPG STGRVVAADA SDLDAVLRSG EPEPDAVLVR
YEPEGDDPRA AARHGVLWAA ALVRRWLEQE ELPGATLVIA TSGAVTVSDD DSVPEPGAAA
MWGVIRCAQA ESPDRFVLLD TDAEPGMLPA VPDNPQLALR GDDVFVPRLS PLAPSALTLP
AGTQRLVPGD GAIDSVAFEP APDVEQPLRA GEVRVDVRAT GVNFRDVLLA LGMYPQKADM
GTEAAGVVTA VGPDVDAFAP GDRVLGLFQG AFAPIAVTDH RLLARVPDGW SDADAAAVPI
AYTTAHYALH DLAGLRAGQS VLIHAAAGGV GMAAVALARR AGAEVLATAG PAKHGTLRAL
GLDDEHIASS RETGFARKFR ERTGGRGVDV VLNSLTGELL DESADLLAED GVFVEMGKTD
LRDAGDFRGR YAPFDLGEAG DDRLGEILRE VVGLLGAGEL DRLPVSAWEL GSAPAALQHM
SRGRHVGKLV LTQPAPVDPD GTVLITGGTG TLGRLLARHL VTEHGVRHLL LVSRRGADAP
GSDELRAEIE DLGASAEIAA CDTADRDALS ALLDGLPRPL TGVVHAAGVL ADGLVTSIDE
PAVEQVLRAK VDAAWNLHEL TANTGLSFFV LFSSAASVLA GPGQGVYAAA NESLNALAAL
RRTRGLPAKA LGWGLWAQAS EMTSGLGDRI ARTGVAALPT ERALALFDSA LRRGGEVVFP
LSINRSALRR AEFVPEVLRG MVRAKLRAAG QAEAAGPNVV DRLAGRSESD QVAGLAELVR
SHAAAVSGYG SADQLPERKA FKDLGFDSLA AVELRNRLGT ATGVRLPSTL VFDHPTPLAV
AEHLRDRLFA ASPAVDIGDR LDELEKALEA LSAEDGHDDV GQRLESLLRR WNSRRADAPS
TSAISEDASD DELFSMLDQR FGGGEDL
