1fxu: Difference between revisions

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PURINE NUCLEOSIDE PHOSPHORYLASE FROM CALF SPLEEN IN COMPLEX WITH N(7)-ACYCLOGUANOSINE INHIBITOR AND A PHOSPHATE ION

OverviewOverview

The calf spleen purine nucleoside phosphorylase (PNP) ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate ion has been crystallized in the cubic space group P2(1)3, with unit-cell parameter a = 94.11 A and one monomer per asymmetric unit. X-ray diffraction data were collected using synchrotron radiation (Station X31, EMBL Outstation, DESY, Hamburg). The crystal structure was refined to a resolution of 2.2 A and R and R(free) values of 17.5 and 24.5%, respectively. The acyclonucleoside inhibitor is bound in the active site in an inverted ('upside-down') orientation of the purine base compared with natural substrates. The side chain of Asp243 forms two hydrogen bonds with the base ring: N(delta) donates a hydrogen to N(3) and O(delta) accepts a hydrogen from the guanine N(2)-amino group. N(1)--H of the base is hydrogen bonded to O(epsilon) of Glu201, while N(9) accepts a hydrogen bond from Thr242 O(gamma). In addition, a water molecule (W417) bridges the N(2)-amino group of the base and O(epsilon) of Glu201. In the phosphate-binding site, a phosphate ion is bound to Ser33, His64, Arg84, His86, Ala116 and Ser220. The acyclic chain of the N(7)-acycloguanosine inhibitor is in a folded conformation and together with a water molecule (W388) occupies the pentose-binding site, with possible hydrogen bonds to Tyr88 O(eta) and His257 N(delta 1). This new binding mode fully accounts for the previously observed substrate properties of 7-beta-D-ribofuranosides of hypoxanthine and guanine. It also provides a new starting point for the design of inhibitors of PNP for therapeutic and other applications.

About this StructureAbout this Structure

1FXU is a Single protein structure of sequence from Bos taurus with , , and as ligands. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Full crystallographic information is available from OCA.

ReferenceReference

Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion., Luic M, Koellner G, Shugar D, Saenger W, Bzowska A, Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):30-6. PMID:11134924

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-[[Image:1fxu.gif|left|200px]]<br /><applet load="1fxu" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1fxu.gif|left|200px]]<br /><applet load="1fxu" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1fxu, resolution 2.20&Aring;" />
 '''PURINE NUCLEOSIDE PHOSPHORYLASE FROM CALF SPLEEN IN COMPLEX WITH N(7)-ACYCLOGUANOSINE INHIBITOR AND A PHOSPHATE ION'''<br />
 ==Overview==
-The calf spleen purine nucleoside phosphorylase (PNP) ternary complex with, an N(7)-acycloguanosine inhibitor and a phosphate ion has been, crystallized in the cubic space group P2(1)3, with unit-cell parameter a =, 94.11 A and one monomer per asymmetric unit. X-ray diffraction data were, collected using synchrotron radiation (Station X31, EMBL Outstation, DESY, Hamburg). The crystal structure was refined to a resolution of 2.2 A and R, and R(free) values of 17.5 and 24.5%, respectively. The acyclonucleoside, inhibitor is bound in the active site in an inverted ('upside-down'), orientation of the purine base compared with natural substrates. The side, chain of Asp243 forms two hydrogen bonds with the base ring: N(delta), donates a hydrogen to N(3) and O(delta) accepts a hydrogen from the, guanine N(2)-amino group. N(1)--H of the base is hydrogen bonded to, O(epsilon) of Glu201, while N(9) accepts a hydrogen bond from Thr242, O(gamma). In addition, a water molecule (W417) bridges the N(2)-amino, group of the base and O(epsilon) of Glu201. In the phosphate-binding site, a phosphate ion is bound to Ser33, His64, Arg84, His86, Ala116 and Ser220., The acyclic chain of the N(7)-acycloguanosine inhibitor is in a folded, conformation and together with a water molecule (W388) occupies the, pentose-binding site, with possible hydrogen bonds to Tyr88 O(eta) and, His257 N(delta 1). This new binding mode fully accounts for the previously, observed substrate properties of 7-beta-D-ribofuranosides of hypoxanthine, and guanine. It also provides a new starting point for the design of, inhibitors of PNP for therapeutic and other applications.
+The calf spleen purine nucleoside phosphorylase (PNP) ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate ion has been crystallized in the cubic space group P2(1)3, with unit-cell parameter a = 94.11 A and one monomer per asymmetric unit. X-ray diffraction data were collected using synchrotron radiation (Station X31, EMBL Outstation, DESY, Hamburg). The crystal structure was refined to a resolution of 2.2 A and R and R(free) values of 17.5 and 24.5%, respectively. The acyclonucleoside inhibitor is bound in the active site in an inverted ('upside-down') orientation of the purine base compared with natural substrates. The side chain of Asp243 forms two hydrogen bonds with the base ring: N(delta) donates a hydrogen to N(3) and O(delta) accepts a hydrogen from the guanine N(2)-amino group. N(1)--H of the base is hydrogen bonded to O(epsilon) of Glu201, while N(9) accepts a hydrogen bond from Thr242 O(gamma). In addition, a water molecule (W417) bridges the N(2)-amino group of the base and O(epsilon) of Glu201. In the phosphate-binding site, a phosphate ion is bound to Ser33, His64, Arg84, His86, Ala116 and Ser220. The acyclic chain of the N(7)-acycloguanosine inhibitor is in a folded conformation and together with a water molecule (W388) occupies the pentose-binding site, with possible hydrogen bonds to Tyr88 O(eta) and His257 N(delta 1). This new binding mode fully accounts for the previously observed substrate properties of 7-beta-D-ribofuranosides of hypoxanthine and guanine. It also provides a new starting point for the design of inhibitors of PNP for therapeutic and other applications.
 ==About this Structure==
-FXU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with MG, ZN, PO4 and GU7 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FXU OCA].
+FXU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=GU7:'>GU7</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FXU OCA].
 ==Reference==
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 [[Category: nucleoside phosphorylase]]
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