HEPB_PEDHD
ID HEPB_PEDHD Reviewed; 772 AA.
AC C6XZB6; Q46080;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Heparin and heparin-sulfate lyase;
DE AltName: Full=Heparin lyase;
DE EC=4.2.2.7;
DE AltName: Full=Heparin-sulfate lyase;
DE EC=4.2.2.8;
DE AltName: Full=Heparinase II;
DE Short=HepII;
DE Flags: Precursor;
GN Name=hepB; OrderedLocusNames=Phep_2408;
OS Pedobacter heparinus (strain ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457
OS / NBRC 12017 / NCIMB 9290 / NRRL B-14731 / HIM 762-3).
OC Bacteria; Bacteroidetes; Sphingobacteriia; Sphingobacteriales;
OC Sphingobacteriaceae; Pedobacter.
OX NCBI_TaxID=485917;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN
RP SEQUENCE OF 85-96; 222-233 AND 500-526, FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457 / NBRC 12017 / NCIMB
RC 9290 / NRRL B-14731 / HIM 762-3;
RX PubMed=8702264; DOI=10.1128/aem.62.8.2723-2734.1996;
RA Su H., Blain F., Musil R.A., Zimmermann J.J., Gu K., Bennett D.C.;
RT "Isolation and expression in Escherichia coli of hepB and hepC, genes
RT coding for the glycosaminoglycan-degrading enzymes heparinase II and
RT heparinase III, respectively, from Flavobacterium heparinum.";
RL Appl. Environ. Microbiol. 62:2723-2734(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457 / NBRC 12017 / NCIMB
RC 9290 / NRRL B-14731 / HIM 762-3;
RX PubMed=21304637; DOI=10.4056/sigs.22138;
RA Han C., Spring S., Lapidus A., Del Rio T.G., Tice H., Copeland A.,
RA Cheng J.F., Lucas S., Chen F., Nolan M., Bruce D., Goodwin L., Pitluck S.,
RA Ivanova N., Mavromatis K., Mikhailova N., Pati A., Chen A., Palaniappan K.,
RA Land M., Hauser L., Chang Y.J., Jeffries C.C., Saunders E., Chertkov O.,
RA Brettin T., Goker M., Rohde M., Bristow J., Eisen J.A., Markowitz V.,
RA Hugenholtz P., Kyrpides N.C., Klenk H.P., Detter J.C.;
RT "Complete genome sequence of Pedobacter heparinus type strain (HIM 762-
RT 3).";
RL Stand. Genomic Sci. 1:54-62(2009).
RN [3]
RP IDENTIFICATION.
RX PubMed=2211596; DOI=10.1016/s0021-9258(17)44833-2;
RA Nader H.B., Porcionatto M.A., Tersariol I.L., Pinhal M.A., Oliveira F.W.,
RA Moraes C.T., Dietrich C.P.;
RT "Purification and substrate specificity of heparitinase I and heparitinase
RT II from Flavobacterium heparinum. Analyses of the heparin and heparan
RT sulfate degradation products by 13C NMR spectroscopy.";
RL J. Biol. Chem. 265:16807-16813(1990).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 27-772 IN COMPLEX WITH PHOSPHATE
RP AND ZINC, GLYCOSYLATION AT THR-134, AND SUBUNIT.
RX PubMed=16565082; DOI=10.1074/jbc.m512055200;
RA Shaya D., Tocilj A., Li Y., Myette J., Venkataraman G., Sasisekharan R.,
RA Cygler M.;
RT "Crystal structure of heparinase II from Pedobacter heparinus and its
RT complex with a disaccharide product.";
RL J. Biol. Chem. 281:15525-15535(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 24-772 IN COMPLEX WITH
RP N-ACETYL-D-GLUCOSAMINE AND ZINC, GLYCOSYLATION AT THR-134, ACTIVE SITE, AND
RP MUTAGENESIS OF HIS-202; TYR-257; HIS-406 AND TYR-429.
RX PubMed=20404324; DOI=10.1074/jbc.m110.101071;
RA Shaya D., Zhao W., Garron M.L., Xiao Z., Cui Q., Zhang Z., Sulea T.,
RA Linhardt R.J., Cygler M.;
RT "Catalytic mechanism of heparinase II investigated by site-directed
RT mutagenesis and the crystal structure with its substrate.";
RL J. Biol. Chem. 285:20051-20061(2010).
CC -!- FUNCTION: Cleaves both heparin and heparan sulfate glycosaminoglycans
CC through a beta-elimination mechanism. Cleaves heparin at alpha-D-
CC GlcNp2S6S(1->4) alpha-L-IdoAp2S and heparan sulfate at alpha-D-
CC GlcNp2Ac(or 2S)6OH(1->4)beta-D-GlcAp. {ECO:0000269|PubMed:8702264}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Elimination of sulfate, appears to act on linkages between N-
CC acetyl-D-glucosamine and uronate. Product is an unsaturated sugar.;
CC EC=4.2.2.8; Evidence={ECO:0000269|PubMed:8702264};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Eliminative cleavage of polysaccharides containing (1->4)-
CC linked D-glucuronate or L-iduronate residues and (1->4)-alpha-linked
CC 2-sulfoamino-2-deoxy-6-sulfo-D-glucose residues to give
CC oligosaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl
CC groups at their non-reducing ends.; EC=4.2.2.7;
CC Evidence={ECO:0000269|PubMed:8702264};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16565082,
CC ECO:0000269|PubMed:20404324}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:8702264}.
CC -!- SIMILARITY: Belongs to the polysaccharide lyase 12 family.
CC {ECO:0000305}.
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DR EMBL; U27585; AAB18277.1; -; Genomic_DNA.
DR EMBL; CP001681; ACU04612.1; -; Genomic_DNA.
DR RefSeq; WP_015808224.1; NZ_AQGK01000001.1.
DR PDB; 2FUQ; X-ray; 2.15 A; A/B=27-772.
DR PDB; 2FUT; X-ray; 2.30 A; A/B=25-772.
DR PDB; 3E7J; X-ray; 2.10 A; A/B=24-772.
DR PDB; 3E80; X-ray; 2.35 A; A/B/C=24-772.
DR PDBsum; 2FUQ; -.
DR PDBsum; 2FUT; -.
DR PDBsum; 3E7J; -.
DR PDBsum; 3E80; -.
DR AlphaFoldDB; C6XZB6; -.
DR SMR; C6XZB6; -.
DR STRING; 485917.Phep_2408; -.
DR CAZy; PL21; Polysaccharide Lyase Family 21.
DR iPTMnet; C6XZB6; -.
DR EnsemblBacteria; ACU04612; ACU04612; Phep_2408.
DR KEGG; phe:Phep_2408; -.
DR eggNOG; COG5652; Bacteria.
DR HOGENOM; CLU_389651_0_0_10; -.
DR OMA; VARTGWN; -.
DR OrthoDB; 442785at2; -.
DR BioCyc; MetaCyc:MON-19211; -.
DR Proteomes; UP000000852; Chromosome.
DR GO; GO:0042597; C:periplasmic space; TAS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0047488; F:heparin lyase activity; IDA:UniProtKB.
DR GO; GO:0015021; F:heparin-sulfate lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030211; P:heparin catabolic process; IDA:UniProtKB.
DR Gene3D; 1.50.10.100; -; 1.
DR InterPro; IPR008929; Chondroitin_lyas.
DR InterPro; IPR012480; Hepar_II_III.
DR InterPro; IPR040925; HepII_C.
DR InterPro; IPR032518; HepII_N.
DR Pfam; PF16332; DUF4962; 1.
DR Pfam; PF07940; Hepar_II_III; 1.
DR Pfam; PF18675; HepII_C; 1.
DR SUPFAM; SSF48230; SSF48230; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Glycoprotein; Lyase;
KW Metal-binding; Periplasm; Reference proteome; Signal; Zinc.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:8702264"
FT CHAIN 26..772
FT /note="Heparin and heparin-sulfate lyase"
FT /id="PRO_5000144613"
FT ACT_SITE 202
FT /evidence="ECO:0000305|PubMed:20404324"
FT ACT_SITE 257
FT /evidence="ECO:0000305|PubMed:20404324"
FT ACT_SITE 406
FT /evidence="ECO:0000305|PubMed:20404324"
FT BINDING 96
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 145
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 148
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 196
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 205
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 261
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 307
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 405
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16565082,
FT ECO:0000269|PubMed:20404324"
FT BINDING 425
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16565082,
FT ECO:0000269|PubMed:20404324"
FT BINDING 429
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT BINDING 436..437
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT BINDING 451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16565082,
FT ECO:0000269|PubMed:20404324"
FT BINDING 470
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000269|PubMed:20404324"
FT CARBOHYD 134
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000269|PubMed:16565082,
FT ECO:0000269|PubMed:20404324"
FT MUTAGEN 202
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20404324"
FT MUTAGEN 257
FT /note="Y->F: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20404324"
FT MUTAGEN 406
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20404324"
FT MUTAGEN 429
FT /note="Y->A,F: Impaired catalytic activity."
FT /evidence="ECO:0000269|PubMed:20404324"
FT CONFLICT 505
FT /note="R -> V (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 758
FT /note="A -> P (in Ref. 1; AAB18277)"
FT /evidence="ECO:0000305"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2FUT"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 61..66
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 71..80
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 95..99
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 104..118
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 121..137
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 147..163
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 170..184
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 211..218
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 219..222
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 225..236
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 238..245
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 254..275
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 283..289
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 290..294
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 319..329
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 349..355
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 375..378
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 380..385
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 392..397
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 414..423
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 439..443
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 451..457
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 468..472
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 496..500
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 501..503
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 508..516
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 522..529
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 538..549
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:2FUQ"
FT STRAND 557..569
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 572..582
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 585..587
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 590..594
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 602..611
FT /evidence="ECO:0007829|PDB:3E7J"
FT HELIX 613..615
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 616..623
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 624..628
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 651..660
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 663..675
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 685..688
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 690..697
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 700..705
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 715..719
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 721..723
FT /evidence="ECO:0007829|PDB:2FUQ"
FT STRAND 725..729
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 734..741
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 744..752
FT /evidence="ECO:0007829|PDB:3E7J"
FT TURN 754..756
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 759..763
FT /evidence="ECO:0007829|PDB:3E7J"
FT STRAND 765..771
FT /evidence="ECO:0007829|PDB:3E7J"
SQ SEQUENCE 772 AA; 87626 MW; 66D9752035421B99 CRC64;
MKRQLYLYVI FVVVELMVFT TKGYSQTKAD VVWKDVDGVS MPIPPKTHPR LYLREQQVPD
LKNRMNDPKL KKVWADMIKM QEDWKPADIP EVKDFRFYFN QKGLTVRVEL MALNYLMTKD
PKVGREAITS IIDTLETATF KPAGDISRGI GLFMVTGAIV YDWCYDQLKP EEKTRFVKAF
VRLAKMLECG YPPVKDKSIV GHASEWMIMR DLLSVGIAIY DEFPEMYNLA AGRFFKEHLV
ARNWFYPSHN YHQGMSYLNV RFTNDLFALW ILDRMGAGNV FNPGQQFILY DAIYKRRPDG
QILAGGDVDY SRKKPKYYTM PALLAGSYYK DEYLNYEFLK DPNVEPHCKL FEFLWRDTQL
GSRKPDDLPL SRYSGSPFGW MIARTGWGPE SVIAEMKVNE YSFLNHQHQD AGAFQIYYKG
PLAIDAGSYT GSSGGYNSPH NKNFFKRTIA HNSLLIYDPK ETFSSSGYGG SDHTDFAAND
GGQRLPGKGW IAPRDLKEML AGDFRTGKIL AQGFGPDNQT PDYTYLKGDI TAAYSAKVKE
VKRSFLFLNL KDAKVPAAMI VFDKVVASNP DFKKFWLLHS IEQPEIKGNQ ITIKRTKNGD
SGMLVNTALL PDAANSNITS IGGKGKDFWV FGTNYTNDPK PGTDEALERG EWRVEITPKK
AAAEDYYLNV IQIADNTQQK LHEVKRIDGD KVVGVQLADR IVTFSKTSET VDRPFGFSVV
GKGTFKFVMT DLLPGTWQVL KDGKILYPAL SAKGDDGALY FEGTEGTYRF LR
