EzCatDB: S00375
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DB codeS00375
RLCP classification2.40.18500.20 : Phosphorolysis
CATH domainDomain 13.40.50.1580 : Rossmann foldCatalytic domain
E.C.2.4.2.1
CSA1ula
MACiEM0017

CATH domainRelated DB codes (homologues)
3.40.50.1580 : Rossmann foldS00510,S00376

Enzyme Name
UniProtKBKEGG

P55859P00491P81989
Protein namePurine nucleoside phosphorylasePurine nucleoside phosphorylasePurine nucleoside phosphorylasepurine-nucleoside phosphorylase
inosine phosphorylase
PNPase
PUNPI
PUNPII
inosine-guanosine phosphorylase
nucleotide phosphatase
purine deoxynucleoside phosphorylase
purine deoxyribonucleoside phosphorylase
purine nucleoside phosphorylase
purine ribonucleoside phosphorylase
SynonymsPNP
EC 2.4.2.1
Inosine phosphorylase
PNP
EC 2.4.2.1
Inosine phosphorylase
PNP
EC 2.4.2.1
Inosine phosphorylase
RefSeq
NP_000261.2 (Protein)
NM_000270.3 (DNA/RNA sequence)

PfamPF01048 (PNP_UDP_1)
[Graphical view]
PF01048 (PNP_UDP_1)
[Graphical view]
PF01048 (PNP_UDP_1)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism
MAP00240Pyrimidine metabolism
MAP00760Nicotinate and nicotinamide metabolism

UniProtKB:Accession NumberP55859P00491P81989
Entry namePNPH_BOVINPNPH_HUMANPUNA_CELSP
ActivityPurine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.
SubunitHomotrimer.Homotrimer.Homotrimer.
Subcellular location


Cofactor



Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC15586C00009C15587C00620
CompoundPurine nucleosideOrthophosphatePurinealpha-D-Ribose 1-phosphate
Typenucleosidephosphate group/phosphate ionaromatic ring (with nitrogen atoms)carbohydrate,phosphate group/phosphate ion
ChEBI18255
26078
35589
35588
35586
17258
16300
PubChem68368
22486802
1004
1044
439236
            
1a9oAUnboundBound:PO4UnboundUnbound
1a9pAAnalogue:9DIBound:PO4UnboundUnbound
1a9qAUnboundAnalogue:SO4Bound:HPAUnbound
1a9rAUnboundAnalogue:SO4Bound:HPAUnbound
1a9sAAnalogue:NOSAnalogue:SO4UnboundUnbound
1a9tAUnboundUnboundBound:HPABound:R1P
1b8nAAnalogue:IMGBound:PO4UnboundUnbound
1b8oAAnalogue:IMHBound:PO4UnboundUnbound
1fxuAAnalogue:GU7Bound:PO4UnboundUnbound
1pbnAUnboundUnboundUnboundUnbound
1qe5AUnboundBound:PO4UnboundUnbound
1qe5BUnboundBound:PO4UnboundUnbound
1qe5CUnboundBound:PO4UnboundUnbound
1ulaAUnboundAnalogue:SO4UnboundUnbound
1ulbAUnboundAnalogue:SO4Bound:GUNUnbound
1vfnAUnboundUnboundBound:HPAUnbound
3pnpAUnboundBound:PO4UnboundUnbound
4pnpAUnboundBound:PO4UnboundUnbound
1c3xAUnboundBound:PO4Analogue:8IGUnbound
1c3xBUnboundBound:PO4Analogue:8IGUnbound
1c3xCUnboundBound:PO4Analogue:8IGUnbound

Active-site residues
pdbCatalytic residuescomment
          
1a9oAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1a9pAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1a9qAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1a9rAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1a9sAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1a9tAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1b8nAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1b8oAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1fxuAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1pbnAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1qe5AGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 
1qe5BGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 
1qe5CGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 
1ulaAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1ulbAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1vfnAGLU 201;ASN 243(Base binding);SER 33;      ;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
3pnpAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;       (Ribose)
invisible H257
4pnpAGLU 201;ASN 243(Base binding);SER 33;HIS 64;ARG  84;HIS  86;SER 220(Phosphate);TYR  88;HIS 257(Ribose)
 
1c3xAGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 
1c3xBGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 
1c3xCGLU 204;ASN 246(Base binding);SER 46;      ;ARG 103;HIS 105;SER 223(Phosphate);TYR 107;HIS 258(Ribose)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Fig.7, Fig.9, p.11746-117473
[7]Fig.8, p.7144-71452
[9]Fig.5, p.1248-12503
[11]Fig.12
[14]Fig.5, Fig.7, p.142
[15]Fig.12

references
[1]
PubMed ID2104852
JournalJ Biol Chem
Year1990
Volume265
Pages1812-20
AuthorsEalick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE Jr, et al
TitleThree-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution.
Related UniProtKBP00491
[2]
PubMed ID1763067
JournalProc Natl Acad Sci U S A
Year1991
Volume88
Pages11540-4
AuthorsEalick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd
TitleApplication of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.
Related PDB1ula,1ulb
[3]
PubMed ID7607309
JournalFEBS Lett
Year1995
Volume367
Pages214-8
AuthorsBzowska A, Luic M, Schroder W, Shugar D, Saenger W, Koellner G
TitleCalf spleen purine nucleoside phosphorylase: purification, sequence and crystal structure of its complex with an N(7)-acycloguanosine inhibitor.
[4]
PubMed ID9020983
JournalJ Mol Biol
Year1997
Volume265
Pages202-16
AuthorsKoellner G, Luic M, Shugar D, Saenger W, Bzowska A
TitleCrystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 A resolution.
Related PDB1vfn
Related UniProtKBP55859
[5]
PubMed ID9305962
JournalBiochemistry
Year1997
Volume36
Pages11725-34
AuthorsErion MD, Takabayashi K, Smith HB, Kessi J, Wagner S, Honger S, Shames SL, Ealick SE
TitlePurine nucleoside phosphorylase. 1. Structure-function studies.
[6]
PubMed ID9305963
JournalBiochemistry
Year1997
Volume36
Pages11735-48
AuthorsErion MD, Stoeckler JD, Guida WC, Walter RL, Ealick SE
TitlePurine nucleoside phosphorylase. 2. Catalytic mechanism.
[7]
PubMed ID9585525
JournalBiochemistry
Year1998
Volume37
Pages7135-46
AuthorsMao C, Cook WJ, Zhou M, Federov AA, Almo SC, Ealick SE
TitleCalf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues.
Related PDB1a9o,1a9p,1a9q,1a9r,1a9s,1a9t,1pbn
[8]
PubMed ID10404592
JournalStructure Fold Des
Year1999
Volume7
Pages629-41
AuthorsAppleby TC, Erion MD, Ealick SE
TitleThe structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis.
[9]
PubMed ID10600382
JournalJ Mol Biol
Year1999
Volume294
Pages1239-55
AuthorsTebbe J, Bzowska A, Wielgus-Kutrowska B, Schroder W, Kazimierczuk Z, Shugar D, Saenger W, Koellner G
TitleCrystal structure of the purine nucleoside phosphorylase (PNP) from Cellulomonas sp. and its implication for the mechanism of trimeric PNPs.
Related PDB1qe5,1c3x
Related UniProtKBP81989
[10]
PubMed ID11134924
JournalActa Crystallogr D Biol Crystallogr
Year2001
Volume57
Pages30-6
AuthorsLuic M, Koellner G, Shugar D, Saenger W, Bzowska A
TitleCalf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion.
Related PDB1fxu
[11]
PubMed ID11170405
JournalBiochemistry
Year2001
Volume40
Pages853-60
AuthorsFedorov A, Shi W, Kicska G, Fedorov E, Tyler PC, Furneaux RH, Hanson JC, Gainsford GJ, Larese JZ, Schramm VL, Almo SC
TitleTransition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis.
Related PDB1b8o,1b8n
[12]
PubMed ID11444966
JournalBiochemistry
Year2001
Volume40
Pages8204-15
AuthorsShi W, Basso LA, Santos DS, Tyler PC, Furneaux RH, Blanchard JS, Almo SC, Schramm VL
TitleStructures of purine nucleoside phosphorylase from Mycobacterium tuberculosis in complexes with immucillin-H and its pieces.
[13]
PubMed ID11591349
JournalStructure (Camb)
Year2001
Volume9
Pages941-53
AuthorsLee JE, Cornell KA, Riscoe MK, Howell PL
TitleStructure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases.
[14]
PubMed ID11743878
JournalBiochem J
Year2002
Volume361
Pages1-25
AuthorsPugmire MJ, Ealick SE
TitleStructural analyses reveal two distinct families of nucleoside phosphorylases.
[15]
PubMed ID12463747
JournalBiochemistry
Year2002
Volume41
Pages14489-98
AuthorsKicska GA, Tyler PC, Evans GB, Furneaux RH, Shi W, Fedorov A, Lewandowicz A, Cahill SM, Almo SC, Schramm VL
TitleAtomic dissection of the hydrogen bond network for transition-state analogue binding to purine nucleoside phosphorylase.

comments
The enzymes of this entry corresponds to the Trimeric subunit members of nucleoside phosphorylase family-I [14].
The literature [14] summarized the proposed catalytic mechanism of the enzyme. Beta-nucleoside binds in a high-energy (anticlinal torsion angle of the glycosidic bond, with the ribose moiety in the uncommon C-4'-endo sugar pucker), according to the literature [6]. This high-energy conformation produces steric strain, which induces glycosidic cleavage. The glycosidic bond is weakened further as electrons flow from O-4' of the ribose to the purine ring, resulting in an oxocarbenium ion that is stabilized by the negative charges of the phosphate ion. The phosphate ion binds on the alpha-side of the ribose ring, where it is postioned to participate in an SN1 nucleophilic attack at the C-1' position. The flow of electrons from the glycosidic bond to the purine ring is probably stabilized by active site residue (Asn) interactions at N-7 position of the purine base.

createdupdated
2002-07-122011-09-27
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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