PDBsum entry 1l1q

Transferase

PDB id: 1l1q

Contents

Protein chain

181 a.a. *

Ligands

SO4 ×3

9DA

Waters ×89

* Residue conservation analysis

PDB id:

1l1q

Name:

Transferase

Title:

Crystal structure of aprtase from giardia lamblia complexed with 9- deazaadenine

Structure:

Adenine phosphoribosyltransferase. Chain: a. Engineered: yes

Source:

Giardia intestinalis. Organism_taxid: 5741. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

1.85Å R-factor: 0.219 R-free: 0.251

Authors:

W.Shi,A.E.Sarver,C.C.Wang,K.S.Tanaka,S.C.Almo,V.L.Schramm

Key ref:

W.Shi et al. (2002). Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration. J Biol Chem, 277, 39981-39988. PubMed id: 12171925 DOI: 10.1074/jbc.M205596200

Date:

19-Feb-02 Release date: 27-Nov-02

Protein chain

Q967M2  (Q967M2_GIAIN) -  Adenine phosphoribosyltransferase from Giardia intestinalis

Seq: 180 a.a.

Struc: 181 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.2.7 - adenine phosphoribosyltransferase.
• Pathway: Ribose activation
• Reaction: AMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + adenine

AMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + adenine (Bound ligand (Het Group name = 9DA) matches with 81.82% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M205596200

J Biol Chem 277:39981-39988 (2002)

PubMed id: 12171925

Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration.

W.Shi, A.E.Sarver, C.C.Wang, K.S.Tanaka, S.C.Almo, V.L.Schramm.

ABSTRACT

The adenine phosphoribosyltransferase (APRTase) from Giardia lamblia was co-crystallized with 9-deazaadenine and sulfate or with 9-deazaadenine and Mg-phosphoribosylpyrophosphate. The complexes were solved and refined to 1.85 and 1.95 A resolution. Giardia APRTase is a symmetric homodimer with the monomers built around Rossman fold cores, an element common to all known purine phosphoribosyltransferases. The catalytic sites are capped with a small hood domain that is unique to the APRTases. These structures reveal several features relevant to the catalytic function of APRTase: 1) a non-proline cis peptide bond (Glu(61)-Ser(62)) is required to form the pyrophosphate binding site in the APRTase.9dA.MgPRPP complex but is a trans peptide bond in the absence of pyrophosphate group, as observed in the APRTase.9dA.SO4 complex; 2) a catalytic site loop is closed and fully ordered in both complexes, with Glu(100) from the catalytic loop acting as the acid/base for protonation/deprotonation of N-7 of the adenine ring; 3) the pyrophosphoryl charge is neutralized by a single Mg2+ ion and Arg(63), in contrast to the hypoxanthine-guanine phosphoribosyltransferases, which use two Mg2+ ions; and 4) the nearest structural neighbors to APRTases are the orotate phosphoribosyltransferases, suggesting different paths of evolution for adenine relative to other purine PRTases. An overlap comparison of AMP and 9-deazaadenine plus Mg-PRPP at the catalytic sites of APRTases indicated that reaction coordinate motion involves a 2.1-A excursion of the ribosyl anomeric carbon, whereas the adenine ring and the 5-phosphoryl group remained fixed. G. lamblia APRTase therefore provides another example of nucleophilic displacement by electrophile migration.

Selected figure(s)

Figure 5.
Fig. 5. Peptide conformation of Glu61-Ser62. a, stereoview of trans conformation of Glu61-Ser62 in the Giardia APRTase·9dA·SO[4] complex. The peptide segment connecting Glu61 and Ser62 is stabilized in the trans conformation by a sulfate ion. b, stereoview of the cis conformation of the same peptide in APRTase·9dA·MgPRPP complex. The unusual cis conformation in the peptide link between Glu61 and Ser62 orients the amide nitrogen atoms of Ser62 and Arg63 to bind PRPP.

Figure 7.
Fig. 7. Hydrogen bond network in Giardia APRTase·9dA·MgPRPP complex. Distances (<3.2 Å) are in angstroms.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 39981-39988) copyright 2002.

Figures were selected by an automated process.