1FXU

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

Summary for 1FXU

• Entry DOI: 10.2210/pdb1fxu/pdb
• Related: 1VFN
• Descriptor: PURINE NUCLEOSIDE PHOSPHORYLASE, MAGNESIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: glycosyltransferase, nucleoside phosphorylase, transferase
• Biological source: Bos taurus (cattle)
• Cellular location: Cytoplasm, cytoskeleton : P55859
• Total number of polymer chains: 1
• Total formula weight: 32517.44

Authors

Luic, M.,Bzowska, A.,Shugar, D.,Saenger, W.,Koellner, G. (deposition date: 2000-09-27, release date: 2000-10-18, Last modification date: 2024-02-07)

Primary citation

Luic, M.,Koellner, G.,Shugar, D.,Saenger, W.,Bzowska, A.
Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion.
Acta Crystallogr.,Sect.D, 57:30-36, 2001

PubMed Abstract: 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.

PubMed: 11134924
DOI: 10.1107/S0907444900014402

Experimental method

X-RAY DIFFRACTION (2.2 Å)