PKS13_MYCTU
ID PKS13_MYCTU Reviewed; 1733 AA.
AC I6X8D2;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Polyketide synthase Pks13 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:19436070, ECO:0000269|PubMed:25467124};
GN Name=pks13 {ECO:0000312|EMBL:CCP46629.1};
GN OrderedLocusNames=Rv3800c {ECO:0000312|EMBL:CCP46629.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP PHOSPHOPANTETHEINYLATION BY PPTT.
RX PubMed=16709676; DOI=10.1073/pnas.0511129103;
RA Chalut C., Botella L., de Sousa-D'Auria C., Houssin C., Guilhot C.;
RT "The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital
RT processes of Mycobacteria.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:8511-8516(2006).
RN [3]
RP FUNCTION, REACTION MECHANISM, ACTIVITY REGULATION, PATHWAY, DOMAIN, AND
RP PHOSPHOPANTETHEINYLATION AT SER-55 AND SER-1266.
RC STRAIN=H37Rv;
RX PubMed=19436070; DOI=10.1074/jbc.m109.006940;
RA Gavalda S., Leger M., van der Rest B., Stella A., Bardou F., Montrozier H.,
RA Chalut C., Burlet-Schiltz O., Marrakchi H., Daffe M., Quemard A.;
RT "The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in
RT Mycobacterium tuberculosis.";
RL J. Biol. Chem. 284:19255-19264(2009).
RN [4]
RP FUNCTION.
RX PubMed=19477415; DOI=10.1016/j.chembiol.2009.03.012;
RA Leger M., Gavalda S., Guillet V., van der Rest B., Slama N., Montrozier H.,
RA Mourey L., Quemard A., Daffe M., Marrakchi H.;
RT "The dual function of the Mycobacterium tuberculosis FadD32 required for
RT mycolic acid biosynthesis.";
RL Chem. Biol. 16:510-519(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP FUNCTION, PATHWAY, IDENTIFICATION AS A DRUG TARGET, AND MUTAGENESIS OF
RP PHE-79.
RX PubMed=23770708; DOI=10.1038/nchembio.1277;
RA Wilson R., Kumar P., Parashar V., Vilcheze C., Veyron-Churlet R.,
RA Freundlich J.S., Barnes S.W., Walker J.R., Szymonifka M.J., Marchiano E.,
RA Shenai S., Colangeli R., Jacobs W.R. Jr., Neiditch M.B., Kremer L.,
RA Alland D.;
RT "Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid
RT biosynthesis.";
RL Nat. Chem. Biol. 9:499-506(2013).
RN [7]
RP FUNCTION, REACTION MECHANISM, PATHWAY, ACTIVE SITE, AND MUTAGENESIS OF
RP SER-1533.
RX PubMed=25467124; DOI=10.1016/j.chembiol.2014.10.011;
RA Gavalda S., Bardou F., Laval F., Bon C., Malaga W., Chalut C., Guilhot C.,
RA Mourey L., Daffe M., Quemard A.;
RT "The polyketide synthase Pks13 catalyzes a novel mechanism of lipid
RT transfer in mycobacteria.";
RL Chem. Biol. 21:1660-1669(2014).
RN [8]
RP IDENTIFICATION AS A DRUG TARGET, AND VARIANTS LYS-1640; SER-1640; GLY-1644
RP AND VAL-1667.
RX PubMed=29328655; DOI=10.1021/acs.jmedchem.7b01319;
RA Zhang W., Lun S., Wang S.H., Jiang X.W., Yang F., Tang J., Manson A.L.,
RA Earl A.M., Gunosewoyo H., Bishai W.R., Yu L.F.;
RT "Identification of novel coumestan derivatives as polyketide synthase 13
RT inhibitors against Mycobacterium tuberculosis.";
RL J. Med. Chem. 61:791-803(2018).
RN [9]
RP IDENTIFICATION AS A DRUG TARGET.
RX PubMed=30875203; DOI=10.1021/acs.jmedchem.9b00010;
RA Zhang W., Lun S., Liu L.L., Xiao S., Duan G., Gunosewoyo H., Yang F.,
RA Tang J., Bishai W.R., Yu L.F.;
RT "Identification of novel coumestan derivatives as polyketide synthase 13
RT inhibitors against Mycobacterium tuberculosis. Part II.";
RL J. Med. Chem. 62:3575-3589(2019).
RN [10] {ECO:0007744|PDB:3TZW, ECO:0007744|PDB:3TZX, ECO:0007744|PDB:3TZY, ECO:0007744|PDB:3TZZ}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 576-1062 OF APO FORM;
RP PALMITOYLATED FORM AND CARBOXYPALMITOYLATED FORM, DOMAIN, AND ACTIVE SITE.
RC STRAIN=H37Rv;
RX PubMed=22825853; DOI=10.1074/jbc.m111.325639;
RA Bergeret F., Gavalda S., Chalut C., Malaga W., Quemard A., Pedelacq J.D.,
RA Daffe M., Guilhot C., Mourey L., Bon C.;
RT "Biochemical and structural study of the atypical acyltransferase domain
RT from the mycobacterial polyketide synthase Pks13.";
RL J. Biol. Chem. 287:33675-33690(2012).
RN [11] {ECO:0007744|PDB:5V3W, ECO:0007744|PDB:5V3X, ECO:0007744|PDB:5V3Y, ECO:0007744|PDB:5V3Z, ECO:0007744|PDB:5V40, ECO:0007744|PDB:5V41, ECO:0007744|PDB:5V42}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1451-1733 OF APO FORM AND IN
RP COMPLEXES WITH INHIBITORS AND OF MUTANT ASN-1607, AND IDENTIFICATION AS A
RP DRUG TARGET.
RX PubMed=28669536; DOI=10.1016/j.cell.2017.06.025;
RA Aggarwal A., Parai M.K., Shetty N., Wallis D., Woolhiser L., Hastings C.,
RA Dutta N.K., Galaviz S., Dhakal R.C., Shrestha R., Wakabayashi S.,
RA Walpole C., Matthews D., Floyd D., Scullion P., Riley J., Epemolu O.,
RA Norval S., Snavely T., Robertson G.T., Rubin E.J., Ioerger T.R.,
RA Sirgel F.A., van der Merwe R., van Helden P.D., Keller P., Bottger E.C.,
RA Karakousis P.C., Lenaerts A.J., Sacchettini J.C.;
RT "Development of a novel lead that targets M.tuberculosis polyketide
RT synthase 13.";
RL Cell 170:249-259.e25(2017).
RN [12] {ECO:0007744|PDB:5XUO}
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 717-827.
RX PubMed=29761048; DOI=10.7717/peerj.4728;
RA Yu M., Dou C., Gu Y., Cheng W.;
RT "Crystallization and structure analysis of the core motif of the Pks13
RT acyltransferase domain from Mycobacterium tuberculosis.";
RL PeerJ 6:e4728-e4728(2018).
RN [13] {ECO:0007744|PDB:6C4Q}
RP X-RAY CRYSTALLOGRAPHY (1.16 ANGSTROMS) OF 1-100.
RG Center for Structural Genomics of Infectious Diseases (CSGID);
RA Minasov G., Shuvalova L., Dubrovska I., Kiryukhina O., Grimshaw S.,
RA Kwon K., Anderson W.F., Satchell K.J.F., Joachimiak A.;
RT "1.16 angstrom resolution crystal structure of acyl carrier protein domain
RT (residues 1-100) of polyketide synthase Pks13 from Mycobacterium
RT tuberculosis.";
RL Submitted (JAN-2018) to the PDB data bank.
RN [14] {ECO:0007744|PDB:6C4V}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1349-1461.
RG Center for Structural Genomics of Infectious Diseases (CSGID);
RA Minasov G., Brunzelle J.S., Shuvalova L., Dubrovska I., Kiryukhina O.,
RA Grimshaw S., Kwon K., Anderson W.F., Satchell K.J.F., Joachimiak A.;
RT "1.9 angstrom resolution crystal structure of acyl carrier protein domain
RT (residues 1350-1461) of polyketide synthase Pks13 from Mycobacterium
RT tuberculosis.";
RL Submitted (JAN-2018) to the PDB data bank.
RN [15] {ECO:0007744|PDB:6D8I, ECO:0007744|PDB:6D8J}
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 10-93.
RA Tang S., Sacchettini J.;
RT "Mycobacterium tuberculosis polyketide synthase 13 N-terminal acyl carrier
RT protein domain.";
RL Submitted (APR-2018) to the PDB data bank.
CC -!- FUNCTION: Involved in the biosynthesis of mycolic acids
CC (PubMed:19436070, PubMed:23770708, PubMed:25467124). Forms, with
CC FadD32, the initiation module of the mycolic condensation system
CC (PubMed:19436070, PubMed:19477415, PubMed:25467124). Synthesizes, in
CC coupled reaction with FadD32, the biosynthetic precursors of mycolic
CC acids, alpha-alkyl beta-ketoacids, via the condensation of two long
CC chain fatty acid derivatives, a very long meromycoloyl-AMP and a
CC shorter 2-carboxyacyl-CoA (PubMed:19436070, PubMed:25467124). The acyl
CC chain of the acyl-AMP produced by FadD32 is specifically transferred
CC onto the N-terminal ACP domain of Pks13, and then transferred onto the
CC KS domain. The extender unit carboxyacyl-CoA is specifically loaded
CC onto the AT domain, which catalyzes the covalent attachment of the
CC carboxyacyl chain to its active site, and its subsequent transfer onto
CC the P-pant arm of the C-terminal ACP domain. The KS domain catalyzes
CC the condensation between the two loaded fatty acyl chains to produce an
CC alpha-alkyl beta-ketothioester linked to the C-ACP domain
CC (PubMed:19436070). Then, the thioesterase-like domain acts as a
CC transacylase and is responsible for both the release and the transfer
CC of the alpha-alkyl beta-ketoacyl chain onto a polyol acceptor molecule,
CC particularly trehalose, leading to the formation of the trehalose
CC monomycolate precursor (PubMed:25467124). {ECO:0000269|PubMed:19436070,
CC ECO:0000269|PubMed:19477415, ECO:0000269|PubMed:23770708,
CC ECO:0000269|PubMed:25467124}.
CC -!- ACTIVITY REGULATION: The presence of FadD32 is necessary for the
CC transfer of the acyl chain from the AMP carrier onto Pks13.
CC {ECO:0000269|PubMed:19436070}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000269|PubMed:19436070, ECO:0000269|PubMed:23770708,
CC ECO:0000269|PubMed:25467124}.
CC -!- DOMAIN: Made of a minimal module holding ketosynthase (KS),
CC acyltransferase (AT), and C-terminal acyl carrier protein (C-ACP)
CC domains, and additional N-terminal ACP (N-ACP) and C-terminal
CC thioesterase-like domains. {ECO:0000269|PubMed:22825853,
CC ECO:0000305|PubMed:19436070}.
CC -!- PTM: 4'-phosphopantetheine is transferred from CoA to specific serines
CC of apo-Pks13 by PptT. {ECO:0000269|PubMed:16709676,
CC ECO:0000269|PubMed:19436070}.
CC -!- MISCELLANEOUS: Identified as a drug target (PubMed:23770708,
CC PubMed:28669536, PubMed:29328655, PubMed:30875203). Fatty acyl-AMP
CC loading is inhibited by thiophene (TP) compounds, which kill
CC Mycobacterium tuberculosis. Overexpression of wild-type Pks13 results
CC in TP resistance, and overexpression of the F79S mutant confers high
CC resistance (PubMed:23770708). Structure-guided methods identified a
CC highly potent and very safe lead compound, TAM16, a benzofuran class
CC inhibitor that targets the thioesterase activity (PubMed:28669536). The
CC thioesterase-like domain is inhibited by coumestan derivatives that
CC possess excellent anti-tuberculosis activity against both the drug-
CC susceptible and drug-resistant Mtb strains (PubMed:29328655,
CC PubMed:30875203). {ECO:0000269|PubMed:23770708,
CC ECO:0000269|PubMed:28669536, ECO:0000269|PubMed:29328655,
CC ECO:0000269|PubMed:30875203}.
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DR EMBL; AL123456; CCP46629.1; -; Genomic_DNA.
DR RefSeq; NP_218317.1; NC_000962.3.
DR RefSeq; WP_003902557.1; NZ_NVQJ01000022.1.
DR PDB; 3TZW; X-ray; 2.60 A; A=576-1062.
DR PDB; 3TZX; X-ray; 2.30 A; A/B=576-1062.
DR PDB; 3TZY; X-ray; 2.20 A; A/B=576-1062.
DR PDB; 3TZZ; X-ray; 2.49 A; A/B=576-1062.
DR PDB; 5V3W; X-ray; 1.72 A; A/B=1451-1733.
DR PDB; 5V3X; X-ray; 1.94 A; A/B=1451-1733.
DR PDB; 5V3Y; X-ray; 1.98 A; A/B=1451-1733.
DR PDB; 5V3Z; X-ray; 1.88 A; A/B=1451-1733.
DR PDB; 5V40; X-ray; 1.99 A; A/B=1451-1733.
DR PDB; 5V41; X-ray; 2.05 A; A/B=1451-1733.
DR PDB; 5V42; X-ray; 1.99 A; A/B=1451-1733.
DR PDB; 5XUO; X-ray; 2.59 A; A=717-827.
DR PDB; 6C4Q; X-ray; 1.16 A; A=1-100.
DR PDB; 6C4V; X-ray; 1.90 A; A=1349-1461.
DR PDB; 6D8I; X-ray; 1.65 A; A=10-93.
DR PDB; 6D8J; X-ray; 1.63 A; A=10-93.
DR PDB; 7M7V; X-ray; 2.29 A; A/B=1451-1733.
DR PDBsum; 3TZW; -.
DR PDBsum; 3TZX; -.
DR PDBsum; 3TZY; -.
DR PDBsum; 3TZZ; -.
DR PDBsum; 5V3W; -.
DR PDBsum; 5V3X; -.
DR PDBsum; 5V3Y; -.
DR PDBsum; 5V3Z; -.
DR PDBsum; 5V40; -.
DR PDBsum; 5V41; -.
DR PDBsum; 5V42; -.
DR PDBsum; 5XUO; -.
DR PDBsum; 6C4Q; -.
DR PDBsum; 6C4V; -.
DR PDBsum; 6D8I; -.
DR PDBsum; 6D8J; -.
DR PDBsum; 7M7V; -.
DR AlphaFoldDB; I6X8D2; -.
DR SMR; I6X8D2; -.
DR IntAct; I6X8D2; 1.
DR STRING; 83332.Rv3800c; -.
DR BindingDB; I6X8D2; -.
DR ChEMBL; CHEMBL4105939; -.
DR PaxDb; I6X8D2; -.
DR PRIDE; I6X8D2; -.
DR DNASU; 886133; -.
DR GeneID; 886133; -.
DR KEGG; mtu:Rv3800c; -.
DR PATRIC; fig|83332.111.peg.4225; -.
DR TubercuList; Rv3800c; -.
DR eggNOG; COG0236; Bacteria.
DR eggNOG; COG3319; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR OMA; QHRKMAK; -.
DR PhylomeDB; I6X8D2; -.
DR BioCyc; MetaCyc:G185E-8096-MON; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; 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; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..1733
FT /note="Polyketide synthase Pks13"
FT /id="PRO_0000451588"
FT DOMAIN 17..95
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1232..1309
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 118..539
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000305"
FT REGION 548..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..1034
FT /note="Acyltransferase"
FT /evidence="ECO:0000305"
FT REGION 1344..1368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1470..1563
FT /note="Thioesterase-like"
FT /evidence="ECO:0000305"
FT ACT_SITE 287
FT /note="Acyl-thioester intermediate; for beta-ketoacyl
FT synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 801
FT /note="Acyl-ester intermediate; for acyltransferase
FT activity"
FT /evidence="ECO:0000305|PubMed:22825853"
FT ACT_SITE 1533
FT /note="For thioesterase-like activity"
FT /evidence="ECO:0000305|PubMed:25467124"
FT MOD_RES 55
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:19436070"
FT MOD_RES 1266
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:19436070"
FT VARIANT 1640
FT /note="N -> K (coumestan resistant)"
FT /evidence="ECO:0000269|PubMed:29328655"
FT VARIANT 1640
FT /note="N -> S (coumestan resistant)"
FT /evidence="ECO:0000269|PubMed:29328655"
FT VARIANT 1644
FT /note="D -> G (coumestan resistant)"
FT /evidence="ECO:0000269|PubMed:29328655"
FT VARIANT 1667
FT /note="A -> V (coumestan resistant)"
FT /evidence="ECO:0000269|PubMed:29328655"
FT MUTAGEN 79
FT /note="F->S: Confers thiophene resistance."
FT /evidence="ECO:0000269|PubMed:23770708"
FT MUTAGEN 1533
FT /note="S->A: Cannot form alpha-alkyl beta-ketoacids
FT derivatives."
FT /evidence="ECO:0000269|PubMed:25467124"
FT HELIX 12..15
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 20..35
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 55..69
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 75..80
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 84..93
FT /evidence="ECO:0007829|PDB:6C4Q"
FT HELIX 721..732
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 735..751
FT /evidence="ECO:0007829|PDB:5XUO"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 756..761
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 769..789
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 794..796
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 799..801
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 804..810
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 816..823
FT /evidence="ECO:0007829|PDB:5XUO"
FT HELIX 1378..1391
FT /evidence="ECO:0007829|PDB:6C4V"
FT STRAND 1397..1400
FT /evidence="ECO:0007829|PDB:6C4V"
FT HELIX 1407..1421
FT /evidence="ECO:0007829|PDB:6C4V"
FT HELIX 1427..1431
FT /evidence="ECO:0007829|PDB:6C4V"
FT HELIX 1436..1449
FT /evidence="ECO:0007829|PDB:6C4V"
FT STRAND 1456..1460
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1464..1466
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1471..1474
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1481..1484
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1485..1489
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1497..1500
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1507..1522
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1527..1532
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1534..1548
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1553..1560
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1572..1590
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1599..1603
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1607..1619
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1621..1623
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1627..1642
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1643..1645
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1655..1659
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1665..1670
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1672..1675
FT /evidence="ECO:0007829|PDB:5V3W"
FT TURN 1679..1682
FT /evidence="ECO:0007829|PDB:5V3W"
FT TURN 1684..1686
FT /evidence="ECO:0007829|PDB:5V3W"
FT STRAND 1687..1694
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1699..1701
FT /evidence="ECO:0007829|PDB:5V3W"
FT TURN 1705..1707
FT /evidence="ECO:0007829|PDB:5V3W"
FT HELIX 1708..1726
FT /evidence="ECO:0007829|PDB:5V3W"
SQ SEQUENCE 1733 AA; 186446 MW; D6D933468481E86A CRC64;
MADVAESQEN APAERAELTV PEMRQWLRNW VGKAVGKAPD SIDESVPMVE LGLSSRDAVA
MAADIEDLTG VTLSVAVAFA HPTIESLATR IIEGEPETDL AGDDAEDWSR TGPAERVDIA
IVGLSTRFPG EMNTPEQTWQ ALLEGRDGIT DLPDGRWSEF LEEPRLAARV AGARTRGGYL
KDIKGFDSEF FAVAKTEADN IDPQQRMALE LTWEALEHAR IPASSLRGQA VGVYIGSSTN
DYSFLAVSDP TVAHPYAITG TSSSIIANRV SYFYDFHGPS VTIDTACSSS LVAIHQGVQA
LRNGEADVVV AGGVNALITP MVTLGFDEIG AVLAPDGRIK SFSADADGYT RSEGGGMLVL
KRVDDARRDG DAILAVIAGS AVNHDGRSNG LIAPNQDAQA DVLRRAYKDA GIDPRTVDYI
EAHGTGTILG DPIEAEALGR VVGRGRPADR PALLGAVKTN VGHLESAAGA ASMAKVVLAL
QHDKLPPSIN FAGPSPYIDF DAMRLKMITT PTDWPRYGGY ALAGVSSFGF GGANAHVVVR
EVLPRDVVEK EPEPEPEPKA AAEPAEAPTL AGHALRFDEF GNIITDSAVA EEPEPELPGV
TEEALRLKEA ALEELAAQEV TAPLVPLAVS AFLTSRKKAA AAELADWMQS PEGQASSLES
IGRSLSRRNH GRSRAVVLAH DHDEAIKGLR AVAAGKQAPN VFSVDGPVTT GPVWVLAGFG
AQHRKMGKSL YLRNEVFAAW IEKVDALVQD ELGYSVLELI LDDAQDYGIE TTQVTIFAIQ
IALGELLRHH GAKPAAVIGQ SLGEAASAYF AGGLSLRDAT RAICSRSHLM GEGEAMLFGE
YIRLMALVEY SADEIREVFS DFPDLEVCVY AAPTQTVIGG PPEQVDAILA RAEAEGKFAR
KFATKGASHT SQMDPLLGEL TAELQGIKPT SPTCGIFSTV HEGRYIKPGG EPIHDVEYWK
KGLRHSVYFT HGIRNAVDSG HTTFLELAPN PVALMQVALT TADAGLHDAQ LIPTLARKQD
EVSSMVSTMA QLYVYGHDLD IRTLFSRASG PQDYANIPPT RFKRKEHWLP AHFSGDGSTY
MPGTHVALPD GRHVWEYAPR DGNVDLAALV RAAAAHVLPD AQLTAAEQRA VPGDGARLVT
TMTRHPGGAS VQVHARIDES FTLVYDALVS RAGSESVLPT AVGAATAIAV ADGAPVAPET
PAEDADAETL SDSLTTRYMP SGMTRWSPDS GETIAERLGL IVGSAMGYEP EDLPWEVPLI
ELGLDSLMAV RIKNRVEYDF DLPPIQLTAV RDANLYNVEK LIEYAVEHRD EVQQLHEHQK
TQTAEEIARA QAELLHGKVG KTEPVDSEAG VALPSPQNGE QPNPTGPALN VDVPPRDAAE
RVTFATWAIV TGKSPGGIFN ELPRLDDEAA AKIAQRLSER AEGPITAEDV LTSSNIEALA
DKVRTYLEAG QIDGFVRTLR ARPEAGGKVP VFVFHPAGGS TVVYEPLLGR LPADTPMYGF
ERVEGSIEER AQQYVPKLIE MQGDGPYVLV GWSLGGVLAY ACAIGLRRLG KDVRFVGLID
AVRAGEEIPQ TKEEIRKRWD RYAAFAEKTF NVTIPAIPYE QLEELDDEGQ VRFVLDAVSQ
SGVQIPAGII EHQRTSYLDN RAIDTAQIQP YDGHVTLYMA DRYHDDAIMF EPRYAVRQPD
GGWGEYVSDL EVVPIGGEHI QAIDEPIIAK VGEHMSRALG QIEADRTSEV GKQ
