                         SEQUENCE LISTING

<110>  NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH
        (NIPER)
 
<120>  RECOMBINANT HUMAN PARAOXONASE 1 ENZYMES, METHOD OF GENERATION, 
       STABILIZATION AND USES THEREOF

<130>  PCT 1387

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  1065
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rh-PON1(wt)

<400>  1
atggcgaaac tgattgccct gaccctgttg ggcatgggtc tggcgttgtt tcgcaatcat       60

cagagctcgt atcagacgcg tctgaatgcg ctgcgcgagg tgcaaccggt ggaactgcca      120

aattgtaact tggtgaaagg cattgaaacc ggcagcgaag atctggagat tctgccgaat      180

ggtttggcct tcatcagctc gggtctgaaa tatccgggca ttaagtcgtt taatccgaat      240

agcccaggca agatcctgtt aatggatctg aatgaagagg acccgaccgt gttggaactc      300

ggcatcacgg ggtcgaaatt tgatgttagc tcgttcaacc cgcatggcat tagtacgttt      360

accgatgagg acaatgcgat gtacctgctc gtggtcaacc acccagatgc caaatctacc      420

gttgaactgt ttaaattcca ggaggaagaa aaatcgctgt tgcatctcaa gacgattcgc      480

cataaactgt taccaaatct gaacgatatc gtggcggttg gcccggaaca cttctatggt      540

accaatgatc attacttctt agacccgtat ctgcgtagct gggagatgta cctgggcttg      600

gcgtggtcgt atgtggttta ctatagtccg tcggaagtgc gcgtcgtggc cgaaggtttt      660

gattttgcaa acggtattaa tatcagtcca gatggtaaat atgtgtatat tgcggaactg      720

ttggcgcata aaattcacgt ttatgagaag catgccaatt ggaccctgac gccgctgaaa      780

agcttagatt ttaacacctt ggtggataat atttctgtgg atccggagac gggcgatctg      840

tgggttggtt gccatccgaa tggcatgaaa atctttttct atgattcgga aaatccgccg      900

gcgagcgagg tgctgcgtat tcagaatatt ctcaccgaag agccgaaggt cacgcaggtg      960

tacgccgaaa atggtaccgt tctgcagggc tcgacggtgg ccagcgttta taaaggcaag     1020

ctgttaatcg gtaccgtgtt tcataaagcg ctgtattgcg aactc                     1065


<210>  2
<211>  1065
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-A

<400>  2
atggcgaaac tgattgccct gaccctgttg ggcatgggtc tggcgttgtt tcgcaatcat       60

cagagctcgt atcagacgcg tctgaatgcg ctgcgcgagg tgcaaccggt ggaactgcca      120

aattgtaact tggtgaaagg cattgaaacc ggcagcgaag atctggagat tctgccgaat      180

ggtttggcct tcatcagctc gggtctgaaa tatccgggca ttaagtcgtt taatccgaat      240

agcccaggca agatcctgtt aatggatctg aatgaagagg acccgaccgt gttggaactc      300

ggcatcacgg ggtcgaaatt tgatgttagc tcgttcaacc cgtggggcat tagtacgttt      360

accgatgagg acaatgcgat gtacctgctc gtggtcaacc acccagatgc caaatctacc      420

gttgaactgt ttaaattcca ggaggaagaa aaatcgctgt tgcatctcaa gacgattcgc      480

cataaactgt taccaaatct gaacgatatc gtggcggttg gcccggaaca cttctatggt      540

accaatgatc attacttctt agacccgtat ctgcgtagct gggagatgta cctgggcttg      600

gcgtggtcgt atgtggttta ctatagtccg tcggaagtgc gcgtcgtggc cgaaggtttt      660

gattttgcaa acggtattaa tatcagtcca gatggtaaat atgtgtatat tgcggaactg      720

ttggcgcata aaattcacgt ttatgagaag catgccaatt ggaccctgac gccgctgaaa      780

agcttagatt ttaacacctt ggtggataat atttctgtgg atccggagac gggcgatctg      840

tgggttggtt gccatccgaa tggcatgaaa atctttttct atgattcgga aaatccgccg      900

gcgagcgagg tgctgcgtat tcagaatatt ctcaccgaag agccgaaggt cacgcaggtg      960

tacgccgaaa atggtaccgt tctgcagggc tcgacggtgg ccagcgttta taaaggcaag     1020

ctgttaatcg gtaccgtgtt tcataaagcg ctgtattgcg aactc                     1065


<210>  3
<211>  1065
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-B

<400>  3
atggcgaaac tgattgccct gaccctgttg ggcatgggtc tggcgttgtt tcgcaatcat       60

cagagctcgt atcagacgcg tctgaatgcg ctgcgcgagg tgcaaccggt ggaactgcca      120

aattgtaact tggtgaaagg cattgaaacc ggcagcgaag atctggagat tctgccgaat      180

ggtttggcct tcatcagctc gggtctgaaa tatccgggca ttaagtcgtt taatccgaat      240

agcccaggca agatcctgtt aatggatctg aatgaagagg acccgaccgt gttggaactc      300

ggcatcacgg ggtcgaaatt tgatgttagc tcgttcaacc cgtggggcat tagtacgttt      360

accgatgagg acaatgcgat gtacctgctc gtggtcaacc acccagatgc caaatctacc      420

gttgaactgt ttaaattcca ggaggaagaa aaatcgctgt tgcatctcaa gacgattcgc      480

cataaactgt taccaaatct gaacgatatc gtggcggttg gcccggaaca cttctatggt      540

accaatgatc attacttctt agacccgtat ctgaaaagct gggagatgta cctgggcttg      600

gcgtggtcgt atgtggttta ctatagtccg tcggaagtgc gcgtcgtggc cgaaggtttt      660

gattttgcaa acggtattaa tatcagtcca gatggtaaat atgtgtatat tgcggaactg      720

ttggcgcata aaattcacgt ttatgagaag catgccaatt ggaccctgac gccgctgaaa      780

agcttagatt ttaacacctt ggtggataat atttctgtgg atccggagac gggcgatctg      840

tgggttggtt gccatccgaa tggcatgaaa atctttttct atgattcgga aaatccgccg      900

gcgagcgagg tgctgcgtat tcagaatatt ctcaccgaag agccgaaggt cacgcaggtg      960

tacgccgaaa atggtaccgt tctgcagggc tcgacggtgg ccagcgttta taaaggcaag     1020

ctgttaatcg gtaccgtgtt tcataaagcg ctgtattgcg aactc                     1065


<210>  4
<211>  1065
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-C

<400>  4
atggcgaaac tgattgccct gaccctgttg ggcatgggtc tggcgttgtt tcgcaatcat       60

cagagctcgt atcagacgcg tctgaatgcg ctgcgcgagg tgcaaccggt ggaactgcca      120

aattgtaact tggtgaaagg cattgaaacc ggcagcgaag atctggagat tctgccgaat      180

ggtttggcct tcatcagctc gggtctgaaa tatccgggca ttaagtcgtt taatccgaat      240

agcccaggca agatcctgtt aatggatctg aatgaagagg acccgaccgt gttggaactc      300

ggcatcacgg ggtcgaaatt tgatgttagc tcgttcaacc cgtggggcat tagtacgttt      360

accgatgagg acaatgcgat gtacctgctc gtggtcaacc acccagatgc caaatctacc      420

gttgaactgt ttaaattcca ggaggaagaa aaatcgctgt tgcatctcaa gacgattcgc      480

cataaactgt taccaaatct gaacgatatc gtggcggttg gcccggaaca cttctatggt      540

accaatgatc attacttctt agacccgtat ctgcagagct gggagatgta cctgggcttg      600

gcgtggtcgt atgtggttta ctatagtccg tcggaagtgc gcgtcgtggc cgaaggtttt      660

gattttgcaa acggtattaa tatcagtcca gatggtaaat atgtgtatat tgcggaactg      720

ttggcgcata aaattcacgt ttatgagaag catgccaatt ggaccctgac gccgctgaaa      780

agcttagatt ttaacacctt ggtggataat atttctgtgg atccggagac gggcgatctg      840

tgggttggtt gccatccgaa tggcatgaaa atctttttct atgattcgga aaatccgccg      900

gcgagcgagg tgctgcgtat tcagaatatt ctcaccgaag agccgaaggt cacgcaggtg      960

tacgccgaaa atggtaccgt tctgcagggc tcgacggtgg ccagcgttta taaaggcaag     1020

ctgttaatcg gtaccgtgtt tcataaagcg ctgtattgcg aactc                     1065


<210>  5
<211>  1065
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rh-PON1  variant-D

<400>  5
atggcgaaac tgattgccct gaccctgttg ggcatgggtc tggcgttgtt tcgcaatcat       60

cagagctcgt atcagacgcg tctgaatgcg ctgcgcgagg tgcaaccggt ggaactgcca      120

aattgtaact tggtgaaagg cattgaaacc ggcagcgaag atctggagat tctgccgaat      180

ggtttggcct tcatcagctc gggtggtaaa tatccgggca ttaagtcgtt taatccgaat      240

agcccaggca agatcctgtt aatggatctg aatgaagagg acccgaccgt gttggaactc      300

ggcatcacgg ggtcgaaatt tgatgttagc accttcaacc cgtggggcat tagtacgttt      360

accgatgagg acaatgcgat gtacctgctc gtggtcaacc gcccagatgc caaatctacc      420

gttgaactgt ttaaattcca ggaggaagaa aaatcgctgt tgcatctcaa gacgattcgc      480

cataaactgt taccaaatct gaacgatatc gtggcggttg gcccggaaca cttctatggt      540

accaatgatc attacttctt agacccgtat ctgaaaagct gggagatgta cctgggcttg      600

gcgtggtcgt atgtggttta ctatagtccg tcggaagtgc gcgtcgtggc cgaaggtttt      660

gattctgcaa acggtattaa tatcagtcca gatggtaaat atgtgtatat tgcggaactg      720

ttggcgcata aaattcacgt ttatgagaag catgccaatt ggaccctgac gccgctgaaa      780

agcttagatt ttaacacctt ggtggataat atttctgtgg atccggagac gggcgatctg      840

tgggttggtt gccatccgaa tggcatgaaa atctttttct atgattcgga aaatccgccg      900

gcgagcgagg tgctgcgtat tcagaatatt ctcaccgaag agccgaaggt cacgcaggtg      960

tacgccgaaa atggtaccgt tctgcagggc tcgtctgtgg ccagcgttta taaaggcaag     1020

ctgttaatcg gtaccgtgtt tcataaagcg ctgtattgcg aactc                     1065


<210>  6
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rh-PON1(wt)

<400>  6

Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 
1               5                   10                  15      


Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 
            20                  25                  30          


Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 
        35                  40                  45              


Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 
    50                  55                  60                  


Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 
65                  70                  75                  80  


Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 
                85                  90                  95      


Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe 
            100                 105                 110         


Asn Phe His Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 
        115                 120                 125             


Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 
    130                 135                 140                 


Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 
145                 150                 155                 160 


His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 
                165                 170                 175     


His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Arg 
            180                 185                 190         


Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 
        195                 200                 205             


Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn 
    210                 215                 220                 


Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 
225                 230                 235                 240 


Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 
                245                 250                 255     


Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 
            260                 265                 270         


Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 
        275                 280                 285             


Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 
    290                 295                 300                 


Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 
305                 310                 315                 320 


Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val 
                325                 330                 335     


Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 
            340                 345                 350         


Cys Glu Leu 
        355 


<210>  7
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-A

<400>  7

Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 
1               5                   10                  15      


Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 
            20                  25                  30          


Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 
        35                  40                  45              


Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 
    50                  55                  60                  


Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 
65                  70                  75                  80  


Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 
                85                  90                  95      


Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe 
            100                 105                 110         


Asn Phe Trp Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 
        115                 120                 125             


Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 
    130                 135                 140                 


Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 
145                 150                 155                 160 


His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 
                165                 170                 175     


His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Arg 
            180                 185                 190         


Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 
        195                 200                 205             


Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn 
    210                 215                 220                 


Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 
225                 230                 235                 240 


Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 
                245                 250                 255     


Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 
            260                 265                 270         


Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 
        275                 280                 285             


Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 
    290                 295                 300                 


Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 
305                 310                 315                 320 


Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val 
                325                 330                 335     


Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 
            340                 345                 350         


Cys Glu Leu 
        355 


<210>  8
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-B

<400>  8

Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 
1               5                   10                  15      


Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 
            20                  25                  30          


Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 
        35                  40                  45              


Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 
    50                  55                  60                  


Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 
65                  70                  75                  80  


Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 
                85                  90                  95      


Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe 
            100                 105                 110         


Asn Phe Trp Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 
        115                 120                 125             


Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 
    130                 135                 140                 


Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 
145                 150                 155                 160 


His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 
                165                 170                 175     


His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Lys 
            180                 185                 190         


Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 
        195                 200                 205             


Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn 
    210                 215                 220                 


Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 
225                 230                 235                 240 


Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 
                245                 250                 255     


Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 
            260                 265                 270         


Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 
        275                 280                 285             


Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 
    290                 295                 300                 


Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 
305                 310                 315                 320 


Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val 
                325                 330                 335     


Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 
            340                 345                 350         


Cys Glu Leu 
        355 


<210>  9
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-C

<400>  9

Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 
1               5                   10                  15      


Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 
            20                  25                  30          


Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 
        35                  40                  45              


Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 
    50                  55                  60                  


Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 
65                  70                  75                  80  


Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 
                85                  90                  95      


Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe 
            100                 105                 110         


Asn Phe Trp Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 
        115                 120                 125             


Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 
    130                 135                 140                 


Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 
145                 150                 155                 160 


His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 
                165                 170                 175     


His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Gln 
            180                 185                 190         


Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 
        195                 200                 205             


Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn 
    210                 215                 220                 


Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 
225                 230                 235                 240 


Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 
                245                 250                 255     


Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 
            260                 265                 270         


Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 
        275                 280                 285             


Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 
    290                 295                 300                 


Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 
305                 310                 315                 320 


Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val 
                325                 330                 335     


Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 
            340                 345                 350         


Cys Glu Leu 
        355 


<210>  10
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rh-PON1 variant-D

<400>  10

Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 
1               5                   10                  15      


Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 
            20                  25                  30          


Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 
        35                  40                  45              


Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 
    50                  55                  60                  


Ile Ser Ser Gly Gly Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 
65                  70                  75                  80  


Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 
                85                  90                  95      


Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Thr Phe 
            100                 105                 110         


Asn Phe Trp Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 
        115                 120                 125             


Leu Leu Val Val Asn Arg Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 
    130                 135                 140                 


Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 
145                 150                 155                 160 


His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 
                165                 170                 175     


His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Lys 
            180                 185                 190         


Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 
        195                 200                 205             


Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Ser Ala Asn 
    210                 215                 220                 


Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 
225                 230                 235                 240 


Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 
                245                 250                 255     


Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 
            260                 265                 270         


Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 
        275                 280                 285             


Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 
    290                 295                 300                 


Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 
305                 310                 315                 320 


Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Ser Val Ala Ser Val 
                325                 330                 335     


Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 
            340                 345                 350         


Cys Glu Leu 
        355 


