ID PAPA1_CARPA Reviewed; 345 AA. AC P00784; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1988, sequence version 1. DT 27-MAR-2024, entry version 152. DE RecName: Full=Papain; DE EC=3.4.22.2 {ECO:0000269|PubMed:21416241, ECO:0000269|PubMed:23151624, ECO:0000269|PubMed:2404797}; DE AltName: Full=Papaya proteinase I; DE Short=PPI; DE AltName: Allergen=Car p 1; DE Flags: Precursor; OS Carica papaya (Papaya). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; malvids; Brassicales; Caricaceae; Carica. OX NCBI_TaxID=3649; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2881845; DOI=10.1016/0378-1119(86)90080-6; RA Cohen L.W., Coghlan V.M., Dihel L.C.; RT "Cloning and sequencing of papain-encoding cDNA."; RL Gene 48:219-227(1986). RN [2] RP PROTEIN SEQUENCE OF 134-345. RX PubMed=5470818; DOI=10.1016/s0021-9258(18)62954-0; RA Mitchel R.E.J., Chaiken I.M., Smith E.L.; RT "The complete amino acid sequence of papain. Additions and corrections."; RL J. Biol. Chem. 245:3485-3492(1970). RN [3] RP SEQUENCE REVISION TO 197. RX PubMed=5435495; DOI=10.1042/bj1160689; RA Husain S.S., Lowe G.; RT "A reinvestigation of residues 64-68 and 175 in papain. Evidence that RT residues 64 and 175 are asparagine."; RL Biochem. J. 116:689-692(1970). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=2404797; DOI=10.1016/0014-5793(90)80101-n; RA Buttle D.J., Ritonja A., Pearl L.H., Turk V., Barrett A.J.; RT "Selective cleavage of glycyl bonds by papaya proteinase IV."; RL FEBS Lett. 260:195-197(1990). RN [5] RP MUTAGENESIS OF VAL-165; GLY-169 AND LYS-307, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=20304972; DOI=10.1093/protein/gzq016; RA Choudhury D., Biswas S., Roy S., Dattagupta J.K.; RT "Improving thermostability of papain through structure-based protein RT engineering."; RL Protein Eng. Des. Sel. 23:457-467(2010). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND ACTIVE SITES. RX PubMed=5681232; DOI=10.1038/218929a0; RA Drenth J., Jansonius J.N., Koekoek R., Swen H.M., Wolthers B.G.; RT "Structure of papain."; RL Nature 218:929-932(1968). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 134-345 IN COMPLEX WITH SUBSTRATE RP ANALOGS, DISULFIDE BONDS, AND ACTIVE SITES. RX PubMed=952885; DOI=10.1021/bi00662a014; RA Drenth J., Kalk K.H., Swen H.M.; RT "Binding of chloromethyl ketone substrate analogues to crystalline RT papain."; RL Biochemistry 15:3731-3738(1976). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 134-345, DISULFIDE BONDS, AND RP ACTIVE SITES. RX PubMed=6502713; DOI=10.1016/0022-2836(84)90467-4; RA Kamphuis I.G., Kalk K.H., Swarte M.B.A., Drenth J.; RT "Structure of papain refined at 1.65-A resolution."; RL J. Mol. Biol. 179:233-256(1984). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 134-345, AND DISULFIDE BONDS. RX PubMed=2347312; DOI=10.1002/j.1460-2075.1990.tb08321.x; RA Stubbs M.T., Laber B., Bode W., Huber R., Jerala R., Lenarcic B., Turk V.; RT "The refined 2.4 A X-ray crystal structure of recombinant human stefin B in RT complex with the cysteine proteinase papain: a novel type of proteinase RT inhibitor interaction."; RL EMBO J. 9:1939-1947(1990). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 134-345 IN COMPLEX WITH E64, RP DISULFIDE BONDS, ACTIVITY REGULATION, AND ACTIVE SITES. RX PubMed=1860874; DOI=10.2210/pdb1pe6/pdb; RA Yamamoto D., Matsumoto K., Ohishi H., Ishida T., Inoue M., Kitamura K., RA Mizuno H.; RT "Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution."; RL J. Biol. Chem. 266:14771-14777(1991). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS). RX PubMed=1445868; DOI=10.1021/bi00161a007; RA Yamamoto A., Tomoo K., Doi M., Ohishi H., Inoue M., Ishida T., Yamamoto D., RA Tsuboi S., Okamoto H., Okada Y.; RT "Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide RT complex at 1.7-A resolution: noncovalent binding mode of a common sequence RT of endogenous thiol protease inhibitors."; RL Biochemistry 31:11305-11309(1992). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 134-345, AND DISULFIDE BONDS. RA Pickersgill R.W., Harris G.W., Garman E.; RT "Structure of monoclinic papain at 1.60-A resolution."; RL Acta Crystallogr. B 48:59-67(1992). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 134-345 IN COMPLEX WITH RP LEUPEPTIN, DISULFIDE BONDS, AND ACTIVITY REGULATION. RX PubMed=8416808; DOI=10.1016/0014-5793(93)81128-m; RA Schroder E., Phillips C., Garman E., Harlos K., Crawford C.; RT "X-ray crystallographic structure of a papain-leupeptin complex."; RL FEBS Lett. 315:38-42(1993). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 134-345 IN COMPLEX WITH RP INHIBITORS, AND DISULFIDE BONDS. RX PubMed=9804696; DOI=10.1021/jm980249f; RA LaLonde J.M., Zhao B., Smith W.W., Janson C.A., DesJarlais R.L., RA Tomaszek T.A., Carr T.J., Thompson S.K., Oh H.-J., Yamashita D.S., RA Veber D.F., Abdel-Meguid S.S.; RT "Use of papain as a model for the structure-based design of cathepsin K RT inhibitors: crystal structures of two papain-inhibitor complexes RT demonstrate binding to S'-subsites."; RL J. Med. Chem. 41:4567-4576(1998). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 134-345 IN COMPLEX WITH THE RP INHIBITOR CLIK148, AND DISULFIDE BONDS. RX PubMed=10600517; DOI=10.1006/bbrc.1999.1830; RA Tsuge H., Nishimura T., Tada Y., Asao T., Turk D., Turk V., Katunuma N.; RT "Inhibition mechanism of cathepsin L-specific inhibitors based on the RT crystal structure of papain-CLIK148 complex."; RL Biochem. Biophys. Res. Commun. 266:411-416(1999). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 134-345 IN COMPLEX WITH RP INHIBITORS, AND DISULFIDE BONDS. RX PubMed=15357669; DOI=10.1111/j.1399-3011.2004.00181.x; RA Janowski R., Kozak M., Jankowska E., Grzonka Z., Jaskolski M.; RT "Two polymorphs of a covalent complex between papain and a RT diazomethylketone inhibitor."; RL J. Pept. Res. 64:141-150(2004). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 134-345, DISULFIDE BONDS, AND RP ACTIVITY REGULATION. RX PubMed=16754967; DOI=10.1107/s1744309106014849; RA Alphey M.S., Hunter W.N.; RT "High-resolution complex of papain with remnants of a cysteine protease RT inhibitor derived from Trypanosoma brucei."; RL Acta Crystallogr. D 62:504-508(2006). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 134-345, AND DISULFIDE BONDS. RX PubMed=19143838; DOI=10.1111/j.1742-4658.2008.06824.x; RA Redzynia I., Ljunggren A., Bujacz A., Abrahamson M., Jaskolski M., RA Bujacz G.; RT "Crystal structure of the parasite inhibitor chagasin in complex with RT papain allows identification of structural requirements for broad RT reactivity and specificity determinants for target proteases."; RL FEBS J. 276:793-806(2009). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 134-345 IN COMPLEX WITH RP TAROCYSTATIN, DISULFIDE BONDS, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY RP REGULATION. RX PubMed=21416241; DOI=10.1007/s00425-011-1398-8; RA Chu M.-H., Liu K.-L., Wu H.-Y., Yeh K.-W., Cheng Y.-S.; RT "Crystal structure of tarocystatin-papain complex: implications for the RT inhibition property of group-2 phytocystatins."; RL Planta 234:243-254(2011). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF 27-345. RA Roy S., Choudhury D., Biswas S., Dattagupta J.K.; RT "Crystallographic analysis of pro-papain variant elucidates the structural RT basis of the step-wise activation mechanism of the zymogen."; RL Submitted (NOV-2011) to the PDB data bank. RN [21] RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 27-345 OF A THERMOSTABLE MUTANT, RP DISULFIDE BONDS, FUNCTION, MUTAGENESIS OF VAL-165; GLY-169 AND LYS-307, AND RP CATALYTIC ACTIVITY. RX PubMed=23151624; DOI=10.1107/s0907444912038607; RA Roy S., Choudhury D., Aich P., Dattagupta J.K., Biswas S.; RT "The structure of a thermostable mutant of pro-papain reveals its RT activation mechanism."; RL Acta Crystallogr. D 68:1591-1603(2012). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 27-345, AND DISULFIDE BONDS. RA Dutta S., Choudhury D., Roy S., Biswas S.; RT "Pro-peptide regulates the substrate specificity and zymogen activation RT process of papain: A structural and mechanistic insight."; RL Submitted (JUL-2014) to the PDB data bank. RN [23] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 134-345 IN COMPLEX WITH RUTHENIUM RP CONTAINING ORGANOMETALLIC GROUPS, AND DISULFIDE BONDS. RX PubMed=30175357; DOI=10.1039/c8mt00160j; RA Cherrier M.V., Amara P., Talbi B., Salmain M., Fontecilla-Camps J.C.; RT "Crystallographic evidence for unexpected selective tyrosine hydroxylations RT in an aerated achiral Ru-papain conjugate."; RL Metallomics 10:1452-1459(2018). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 134-345, AND DISULFIDE BONDS. RA Kraemer A., Juettner N.E., Fuchsbauer H.-L., Edwards A.M., Arrowsmith C.H., RA Bountra C., Knapp S.; RT "Papain bound to a natural cysteine protease inhibitor from Streptomyces RT mobaraensis."; RL Submitted (NOV-2019) to the PDB data bank. CC -!- FUNCTION: Cysteine proteinase with a high level of diversity in CC substrate specificity, an amino acid bearing a large hydrophobic side CC chain at the P2 position is preferred. {ECO:0000269|PubMed:21416241, CC ECO:0000269|PubMed:23151624, ECO:0000269|PubMed:2404797}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of proteins with broad specificity for peptide CC bonds, but preference for an amino acid bearing a large hydrophobic CC side chain at the P2 position. Does not accept Val in P1'.; CC EC=3.4.22.2; Evidence={ECO:0000269|PubMed:21416241, CC ECO:0000269|PubMed:23151624, ECO:0000269|PubMed:2404797}; CC -!- ACTIVITY REGULATION: Repressed by the active-site-directed cysteine CC protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)- CC butane) produced by Aspergillus japonicus (PubMed:1860874). Inhibited CC by the inhibitor of cysteine proteases from Trypanosoma brucei (TbICP, CC rhodesain) and Colocasia esculenta cv. Kaohsiung no. 1 (CeCPI, CC tarocystatin) (PubMed:16754967, PubMed:21416241). Repressed by CC leupeptin, a peptidic cysteine, serine and threonine protease inhibitor CC (PubMed:8416808). {ECO:0000269|PubMed:1860874, CC ECO:0000269|PubMed:21416241, ECO:0000269|PubMed:8416808, CC ECO:0000303|PubMed:16754967}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.293 mM for L-pyroglutamyl-L-phenylalanyl-L-leucyl-p-nitroanilide CC {ECO:0000269|PubMed:23151624}; CC KM=2.95 mM for N-benzoyl-DL-arginine p-nitroanilide CC {ECO:0000269|PubMed:23151624}; CC KM=1.4 mM for Boc-Ala-Ala-Gly-NHPhNO(2) {ECO:0000269|PubMed:2404797}; CC KM=0.14 mM for Boc-Ala-Ala-Gly-NHMec {ECO:0000269|PubMed:2404797}; CC Note=kcat is 1.021 sec(-1) with CC L-pyroglutamyl-L-phenylalanyl-L-leucyl-p-nitroanilide as substrate CC (PubMed:23151624). kcat is 0.73 sec(-1) with N-benzoyl-DL-arginine CC p-nitroanilide as substrate (PubMed:23151624). kcat is 1.6 sec(-1) CC with Boc-Ala-Ala-Gly-NHPhNO(2) as substrate (PubMed:2404797). kcat is CC 2 sec(-1) with Boc-Ala-Ala-Gly-NHMec as substrate (PubMed:2404797). CC {ECO:0000269|PubMed:23151624, ECO:0000269|PubMed:2404797}; CC pH dependence: CC Optimum pH is 4. {ECO:0000269|PubMed:20304972}; CC Temperature dependence: CC Optimum temperature is 50 degrees Celsius (PubMed:20304972). Unstable CC upon 65 degrees Celsius (PubMed:20304972). CC {ECO:0000269|PubMed:20304972}; CC -!- INTERACTION: CC P00784; P01040: CSTA; Xeno; NbExp=2; IntAct=EBI-8501709, EBI-724303; CC -!- ALLERGEN: Causes an allergic reaction in human. CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE- CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089, CC ECO:0000255|PROSITE-ProRule:PRU10090}. CC -!- WEB RESOURCE: Name=Worthington enzyme manual; CC URL="https://www.worthington-biochem.com/products/papain/manual"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M15203; AAB02650.1; -; mRNA. DR PIR; A26466; PPPA. DR PDB; 1BP4; X-ray; 2.20 A; A=134-345. DR PDB; 1BQI; X-ray; 2.50 A; A=134-345. DR PDB; 1CVZ; X-ray; 1.70 A; A=134-345. DR PDB; 1KHP; X-ray; 2.00 A; A=134-345. DR PDB; 1KHQ; X-ray; 1.60 A; A=134-345. DR PDB; 1PAD; X-ray; 2.80 A; A=134-345. DR PDB; 1PE6; X-ray; 2.10 A; A=134-345. DR PDB; 1PIP; X-ray; 1.70 A; A=134-345. DR PDB; 1POP; X-ray; 2.10 A; A=134-345. DR PDB; 1PPD; X-ray; 2.00 A; A=134-345. DR PDB; 1PPN; X-ray; 1.60 A; A=134-345. DR PDB; 1PPP; X-ray; 1.90 A; A=134-345. DR PDB; 1STF; X-ray; 2.37 A; E=134-345. DR PDB; 2CIO; X-ray; 1.50 A; A=134-345. DR PDB; 2PAD; X-ray; 2.80 A; A=134-345. DR PDB; 3E1Z; X-ray; 1.86 A; B=134-345. DR PDB; 3IMA; X-ray; 2.03 A; A/C=134-345. DR PDB; 3LFY; X-ray; 2.60 A; A/C=134-345. DR PDB; 3TNX; X-ray; 2.62 A; A/C=27-345. DR PDB; 3USV; X-ray; 3.80 A; A/C=27-345. DR PDB; 4PAD; X-ray; 2.80 A; A=134-345. DR PDB; 4QRG; X-ray; 2.50 A; A/B=27-345. DR PDB; 4QRV; X-ray; 1.98 A; A/B=27-345. DR PDB; 4QRX; X-ray; 3.14 A; A/C=27-345. DR PDB; 5PAD; X-ray; 2.80 A; A=134-345. DR PDB; 6H8T; X-ray; 2.10 A; A/J=134-345. DR PDB; 6PAD; X-ray; 2.80 A; A=134-345. DR PDB; 6TCX; X-ray; 1.65 A; AAA=134-345. DR PDB; 9PAP; X-ray; 1.65 A; A=134-345. DR PDBsum; 1BP4; -. DR PDBsum; 1BQI; -. DR PDBsum; 1CVZ; -. DR PDBsum; 1KHP; -. DR PDBsum; 1KHQ; -. DR PDBsum; 1PAD; -. DR PDBsum; 1PE6; -. DR PDBsum; 1PIP; -. DR PDBsum; 1POP; -. DR PDBsum; 1PPD; -. DR PDBsum; 1PPN; -. DR PDBsum; 1PPP; -. DR PDBsum; 1STF; -. DR PDBsum; 2CIO; -. DR PDBsum; 2PAD; -. DR PDBsum; 3E1Z; -. DR PDBsum; 3IMA; -. DR PDBsum; 3LFY; -. DR PDBsum; 3TNX; -. DR PDBsum; 3USV; -. DR PDBsum; 4PAD; -. DR PDBsum; 4QRG; -. DR PDBsum; 4QRV; -. DR PDBsum; 4QRX; -. DR PDBsum; 5PAD; -. DR PDBsum; 6H8T; -. DR PDBsum; 6PAD; -. DR PDBsum; 6TCX; -. DR PDBsum; 9PAP; -. DR AlphaFoldDB; P00784; -. DR PCDDB; P00784; -. DR SMR; P00784; -. DR IntAct; P00784; 1. DR MINT; P00784; -. DR BindingDB; P00784; -. DR ChEMBL; CHEMBL4779; -. DR Allergome; 709; Cari p Papain. DR MEROPS; C01.001; -. DR MEROPS; I29.003; -. DR BRENDA; 3.4.22.2; 1191. DR SABIO-RK; P00784; -. DR EvolutionaryTrace; P00784; -. DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0097655; F:serpin family protein binding; IPI:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd02248; Peptidase_C1A; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR025661; Pept_asp_AS. DR InterPro; IPR000169; Pept_cys_AS. DR InterPro; IPR025660; Pept_his_AS. DR InterPro; IPR013128; Peptidase_C1A. DR InterPro; IPR000668; Peptidase_C1A_C. DR InterPro; IPR039417; Peptidase_C1A_papain-like. DR InterPro; IPR013201; Prot_inhib_I29. DR PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1. DR PANTHER; PTHR12411:SF357; OS01G0971400 PROTEIN; 1. DR Pfam; PF08246; Inhibitor_I29; 1. DR Pfam; PF00112; Peptidase_C1; 1. DR PRINTS; PR00705; PAPAIN. DR SMART; SM00848; Inhibitor_I29; 1. DR SMART; SM00645; Pept_C1; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1. DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1. DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1. PE 1: Evidence at protein level; KW 3D-structure; Allergen; Direct protein sequencing; Disulfide bond; KW Hydrolase; Protease; Signal; Thiol protease; Zymogen. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT PROPEP 19..133 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:5470818" FT /id="PRO_0000026406" FT CHAIN 134..345 FT /note="Papain" FT /id="PRO_0000026407" FT ACT_SITE 158 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088, FT ECO:0000269|PubMed:5681232, ECO:0000269|PubMed:6502713, FT ECO:0000269|PubMed:952885, ECO:0000305|PubMed:1860874, FT ECO:0007744|PDB:1PAD, ECO:0007744|PDB:9PAP" FT ACT_SITE 292 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089, FT ECO:0000269|PubMed:6502713, ECO:0000269|PubMed:952885, FT ECO:0007744|PDB:1PAD, ECO:0007744|PDB:9PAP" FT ACT_SITE 308 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090, FT ECO:0000269|PubMed:5681232, ECO:0000269|PubMed:6502713, FT ECO:0000269|PubMed:952885, ECO:0007744|PDB:1PAD, FT ECO:0007744|PDB:9PAP" FT BINDING 158 FT /ligand="E64" FT /ligand_id="ChEBI:CHEBI:192370" FT /ligand_note="inhibitor; produced by Aspergillus japonicus" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:1860874, FT ECO:0007744|PDB:1PE6, ECO:0007744|PDB:1PPP" FT BINDING 158 FT /ligand="leupeptin" FT /ligand_id="ChEBI:CHEBI:192489" FT /ligand_note="inhibitor; produced by actinomycetes" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:8416808, FT ECO:0007744|PDB:1POP" FT DISULFID 155..196 FT /evidence="ECO:0000269|PubMed:10600517, FT ECO:0000269|PubMed:15357669, ECO:0000269|PubMed:16754967, FT ECO:0000269|PubMed:1860874, ECO:0000269|PubMed:19143838, FT ECO:0000269|PubMed:21416241, ECO:0000269|PubMed:23151624, FT ECO:0000269|PubMed:2347312, ECO:0000269|PubMed:30175357, FT ECO:0000269|PubMed:5470818, ECO:0000269|PubMed:6502713, FT ECO:0000269|PubMed:8416808, ECO:0000269|PubMed:952885, FT ECO:0000269|PubMed:9804696, ECO:0000269|Ref.22, FT ECO:0000269|Ref.24, ECO:0007744|PDB:1BP4, FT ECO:0007744|PDB:1BQI, ECO:0007744|PDB:1CVZ, FT ECO:0007744|PDB:1KHP, ECO:0007744|PDB:1KHQ, FT ECO:0007744|PDB:1PAD, ECO:0007744|PDB:1PE6, FT ECO:0007744|PDB:1PIP, ECO:0007744|PDB:1POP, FT ECO:0007744|PDB:1PPD, ECO:0007744|PDB:1PPN, FT ECO:0007744|PDB:1PPP, ECO:0007744|PDB:1STF, FT ECO:0007744|PDB:2CIO, ECO:0007744|PDB:2PAD, FT ECO:0007744|PDB:3E1Z, ECO:0007744|PDB:3IMA, FT ECO:0007744|PDB:3LFY, ECO:0007744|PDB:3TNX, FT ECO:0007744|PDB:4PAD, ECO:0007744|PDB:4QRG, FT ECO:0007744|PDB:4QRV, ECO:0007744|PDB:4QRX, FT ECO:0007744|PDB:5PAD, ECO:0007744|PDB:6H8T, FT ECO:0007744|PDB:6PAD, ECO:0007744|PDB:6TCX, FT ECO:0007744|PDB:9PAP" FT DISULFID 189..228 FT /evidence="ECO:0000269|PubMed:10600517, FT ECO:0000269|PubMed:15357669, ECO:0000269|PubMed:16754967, FT ECO:0000269|PubMed:1860874, ECO:0000269|PubMed:19143838, FT ECO:0000269|PubMed:21416241, ECO:0000269|PubMed:23151624, FT ECO:0000269|PubMed:2347312, ECO:0000269|PubMed:30175357, FT ECO:0000269|PubMed:5470818, ECO:0000269|PubMed:6502713, FT ECO:0000269|PubMed:8416808, ECO:0000269|PubMed:952885, FT ECO:0000269|PubMed:9804696, ECO:0000269|Ref.22, FT ECO:0000269|Ref.24, ECO:0007744|PDB:1BP4, FT ECO:0007744|PDB:1BQI, ECO:0007744|PDB:1CVZ, FT ECO:0007744|PDB:1KHP, ECO:0007744|PDB:1KHQ, FT ECO:0007744|PDB:1PAD, ECO:0007744|PDB:1PE6, FT ECO:0007744|PDB:1PIP, ECO:0007744|PDB:1POP, FT ECO:0007744|PDB:1PPD, ECO:0007744|PDB:1PPN, FT ECO:0007744|PDB:1PPP, ECO:0007744|PDB:1STF, FT ECO:0007744|PDB:2CIO, ECO:0007744|PDB:2PAD, FT ECO:0007744|PDB:3E1Z, ECO:0007744|PDB:3IMA, FT ECO:0007744|PDB:3LFY, ECO:0007744|PDB:3TNX, FT ECO:0007744|PDB:4PAD, ECO:0007744|PDB:4QRG, FT ECO:0007744|PDB:4QRV, ECO:0007744|PDB:4QRX, FT ECO:0007744|PDB:6H8T, ECO:0007744|PDB:6PAD, FT ECO:0007744|PDB:6TCX, ECO:0007744|PDB:9PAP" FT DISULFID 286..333 FT /evidence="ECO:0000269|PubMed:10600517, FT ECO:0000269|PubMed:15357669, ECO:0000269|PubMed:16754967, FT ECO:0000269|PubMed:1860874, ECO:0000269|PubMed:19143838, FT ECO:0000269|PubMed:21416241, ECO:0000269|PubMed:23151624, FT ECO:0000269|PubMed:2347312, ECO:0000269|PubMed:30175357, FT ECO:0000269|PubMed:5470818, ECO:0000269|PubMed:6502713, FT ECO:0000269|PubMed:8416808, ECO:0000269|PubMed:952885, FT ECO:0000269|PubMed:9804696, ECO:0000269|Ref.22, FT ECO:0000269|Ref.24, ECO:0007744|PDB:1BP4, FT ECO:0007744|PDB:1BQI, ECO:0007744|PDB:1CVZ, FT ECO:0007744|PDB:1KHP, ECO:0007744|PDB:1KHQ, FT ECO:0007744|PDB:1PAD, ECO:0007744|PDB:1PE6, FT ECO:0007744|PDB:1PIP, ECO:0007744|PDB:1POP, FT ECO:0007744|PDB:1PPD, ECO:0007744|PDB:1PPN, FT ECO:0007744|PDB:1PPP, ECO:0007744|PDB:1STF, FT ECO:0007744|PDB:2CIO, ECO:0007744|PDB:2PAD, FT ECO:0007744|PDB:3E1Z, ECO:0007744|PDB:3IMA, FT ECO:0007744|PDB:3LFY, ECO:0007744|PDB:3TNX, FT ECO:0007744|PDB:4PAD, ECO:0007744|PDB:4QRG, FT ECO:0007744|PDB:4QRV, ECO:0007744|PDB:4QRX, FT ECO:0007744|PDB:5PAD, ECO:0007744|PDB:6H8T, FT ECO:0007744|PDB:6PAD, ECO:0007744|PDB:6TCX, FT ECO:0007744|PDB:9PAP" FT MUTAGEN 165 FT /note="V->S: Slightly enhanced thermostability and higher FT optimum temperature; when associated with R-307. Enhanced FT thermostability and higher optimum temperature; when FT associated with S-169 and R-307." FT /evidence="ECO:0000269|PubMed:20304972" FT MUTAGEN 169 FT /note="G->S: Enhanced thermostability and higher optimum FT temperature; when associated with S-165 and R-307." FT /evidence="ECO:0000269|PubMed:20304972" FT MUTAGEN 307 FT /note="K->R: Unstable. Slightly enhanced thermostability FT and higher optimum temperature; when associated with S-165. FT Enhanced thermostability and higher optimum temperature; FT when associated with S-165 and S-169." FT /evidence="ECO:0000269|PubMed:20304972" FT CONFLICT 180 FT /note="E -> Q (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 219..220 FT /note="YP -> PY (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 251 FT /note="E -> Q (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="E -> Q (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 35..38 FT /evidence="ECO:0007829|PDB:4QRV" FT HELIX 41..54 FT /evidence="ECO:0007829|PDB:4QRV" FT HELIX 62..82 FT /evidence="ECO:0007829|PDB:4QRV" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:4QRV" FT TURN 95..98 FT /evidence="ECO:0007829|PDB:4QRV" FT HELIX 101..106 FT /evidence="ECO:0007829|PDB:4QRV" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:4QRV" FT STRAND 119..124 FT /evidence="ECO:0007829|PDB:3TNX" FT TURN 140..144 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:2CIO" FT HELIX 158..175 FT /evidence="ECO:0007829|PDB:2CIO" FT HELIX 183..189 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:1BP4" FT HELIX 195..197 FT /evidence="ECO:0007829|PDB:1CVZ" FT HELIX 201..210 FT /evidence="ECO:0007829|PDB:2CIO" FT TURN 216..218 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:3LFY" FT TURN 230..233 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 241..245 FT /evidence="ECO:0007829|PDB:2CIO" FT HELIX 251..260 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 263..267 FT /evidence="ECO:0007829|PDB:2CIO" FT HELIX 272..275 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 279..282 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 292..300 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:1BQI" FT TURN 315..317 FT /evidence="ECO:0007829|PDB:4QRG" FT STRAND 319..323 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:2CIO" FT HELIX 332..334 FT /evidence="ECO:0007829|PDB:2CIO" FT STRAND 340..343 FT /evidence="ECO:0007829|PDB:2CIO" SQ SEQUENCE 345 AA; 38922 MW; 82D9FB35EDCA12EF CRC64; MAMIPSISKL LFVAICLFVY MGLSFGDFSI VGYSQNDLTS TERLIQLFES WMLKHNKIYK NIDEKIYRFE IFKDNLKYID ETNKKNNSYW LGLNVFADMS NDEFKEKYTG SIAGNYTTTE LSYEEVLNDG DVNIPEYVDW RQKGAVTPVK NQGSCGSCWA FSAVVTIEGI IKIRTGNLNE YSEQELLDCD RRSYGCNGGY PWSALQLVAQ YGIHYRNTYP YEGVQRYCRS REKGPYAAKT DGVRQVQPYN EGALLYSIAN QPVSVVLEAA GKDFQLYRGG IFVGPCGNKV DHAVAAVGYG PNYILIKNSW GTGWGENGYI RIKRGTGNSY GVCGLYTSSF YPVKN //