PDBsum entry 1ukd

Nucleotide monophosphate kinase

PDB id: 1ukd

Contents

Protein chain

193 a.a.

Ligands

UP5

Waters ×129

References listed in PDB file

Key reference

Title

Crystal structure of the complex of ump/cmp kinase from dictyostelium discoideum and the bisubstrate inhibitor p1-(5'-Adenosyl) p5-(5'-Uridyl) pentaphosphate (up5a) and mg2+ at 2.2 a: implications for water-Mediated specificity.

Authors

K.Scheffzek, W.Kliche, L.Wiesmüller, J.Reinstein.

Ref.

Biochemistry, 1996, 35, 9716-9727. [DOI no: 10.1021/bi960642s]

PubMed id

8703943

Abstract

The three-dimensional structure of the UMP/CMP kinase (UK) from the slime mold Dictyostelium discoideum complexed with the specific and asymmetric bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) has been determined at a resolution of 2.2 A. The structure of the enzyme, which has up to 41% sequence homology with known adenylate kinases (AK), represents a closed conformation with the flexible monophosphate binding domain (NMP site) being closed over the uridyl moiety of the dinucleotide. Two water molecules were found within hydrogen-bonding distance to the uracil base. The key residue for the positioning and stabilization of those water molecules appears to be asparagine 97, a residue that is highly specific for AK-homologous UMP kinases, but is almost invariably a glutamine in adenylate kinases. Other residues in this region are highly conserved among AK-related NMP kinases. The catalytic Mg2+ ion is coordinated with octahedral geometry to four water molecules and two oxygens of the phosphate chain of UP5A but has no direct interactions with the protein. The comparison of the geometry of the UKdicty.UP5A.Mg2+ complex with the previously reported structure of the UKyeast.ADP.ADP complex [Müller-Dieckmann & Schulz (1994) J. Mol. Biol. 236, 361-367] suggests that UP5A in our structure mimics an ADP.Mg.UDP biproduct inhibitor rather than an ATP. MG.UMP bisubstrate inhibitor.

Secondary reference #1

Title

High-Resolution structures of adenylate kinase from yeast ligated with inhibitor ap5a, Showing the pathway of phosphoryl transfer.

Authors

U.Abele, G.E.Schulz.

Ref.

Protein Sci, 1995, 4, 1262-1271. [DOI no: 10.1002/pro.5560040702]

PubMed id

7670369

Figure 4.
Fig. 4. Relationbetweenthelengthsofprimaryandsecondaryhydro- genbonds in a-helicesasreferredtothedonoramdeatposition . The plotcontainsalla-helicalH-bonds(Fig. 3) frombothreportedstruc- tures.Averageangles N,-H,. . .0,-4 and N,-H,. . .0,-3 are 161" and I1 I, respectively.

Figure 6.
Fig. 6. BindingofImandMg2+in AK,,, ligated with Ap,A.Mostresidues andtwowatermoleulesarelabeled. Chaincutsaremarked by dots. A: Posi- tion f Mg2+(dot) in an extendedwater cluster.Detailedenvronment of Mg2+ is showninFigures8Band9. : Bind- ing of s suspended between hetird phosphteandAsp89.Imidazoledis- turbsappreciablythewateretworkat theactivecenter.

The above figures are reproduced from the cited reference which is an Open Access publication published by the Protein Society

Secondary reference #2

Title

Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.

Authors

C.Vonrhein, G.J.Schlauderer, G.E.Schulz.

Ref.

Structure, 1995, 3, 483-490. [DOI no: 10.1016/S0969-2126(01)00181-2]

PubMed id

7663945

Figure 1.
Figure 1. Ribbon representation of all established structures used in the movie, including the ligands, which are shown as ball and stick models. 1, AK[eco]:Ap[5]A; 2, AK[eco]; 3, AK1; 4, AK2; 5, AK3:AMP; 6, AK3:AMP; 7, AK[yst]:Ap[5]A; 8, AK[yst]:AMPPCF[2]P; 9, UK[yst]:ADP:ADP. For details see Table 1. Figure 1. Ribbon representation of all established structures used in the movie, including the ligands, which are shown as ball and stick models. 1, AK[eco]:Ap[5]A; 2, AK[eco]; 3, AK1; 4, AK2; 5, AK3:AMP; 6, AK3:AMP; 7, AK[yst]:Ap[5]A; 8, AK[yst]:AMPPCF[2]P; 9, UK[yst]:ADP:ADP. For details see [3]Table 1.

Figure 4.
Figure 4. Picture series 1 to 40 for the LID motion, representing an equally spaced selection from the 90 pictures of the movie. The observed structures, A to G, are indicated. The pictures can be cut out and stapled at the left-hand side to produce a flicker book, as described in the legend for Figure 3. Figure 4. Picture series 1 to 40 for the LID motion, representing an equally spaced selection from the 90 pictures of the movie. The observed structures, A to G, are indicated. The pictures can be cut out and stapled at the left-hand side to produce a flicker book, as described in the legend for [3]Figure 3.

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #3

Title

Substrate specificity and assembly of the catalytic center derived from two structures of ligated uridylate kinase.

Authors

H.J.Müller-Dieckmann, G.E.Schulz.

Ref.

J Mol Biol, 1995, 246, 522-530.

PubMed id

7877173

Secondary reference #4

Title

Crystallization and preliminary X-Ray analysis of ump/cmp-Kinase from dictyostelium discoideum with the specific bisubstrate inhibitor p1-(Adenosine 5')-P5-(Uridine 5')-Pentaphosphate (up5a).

Authors

L.Wiesmüller, K.Scheffzek, W.Kliche, R.S.Goody, A.Wittinghofer, J.Reinstein.

Ref.

FEBS Lett, 1995, 363, 22-24. [DOI no: 10.1016/0014-5793(95)00271-A]

PubMed id

7729545

Secondary reference #5

Title

Cdna-Derived sequence of ump-Cmp kinase from dictyostelium discoideum and expression of the enzyme in escherichia coli.

Authors

L.Wiesmüller, A.A.Noegel, O.Bârzu, G.Gerisch, M.Schleicher.

Ref.

J Biol Chem, 1990, 265, 6339-6345.

PubMed id

2156849