The yeast enzymes involved in UDP-GlcNAc biosynthesis are potential targets for antifungal agents. GNA1, a novel member of the Gcn5-related N-acetyltransferase (GNAT) superfamily, participates in UDP-GlcNAc biosynthesis by catalyzing the formation of GlcNAc6P from AcCoA and GlcN6P. We have solved three crystal structures corresponding to the apo Saccharomyces cerevisiae GNA1, the GNA1-AcCoA, and the GNA1-CoA-GlcNAc6P complexes and have refined them to 2.4, 1.3, and 1.8 Å resolution, respectively. These structures not only reveal a stable, %-intertwined, dimeric assembly with the GlcNAc6P binding site located at the dimer interface but also shed light on the catalytic machinery of GNA1 at an atomic level. Hence, they broaden our understanding of structural features required for GNAT activity, provide structural details for related aminoglycosideN-acetyltransferases, and highlight the adaptability of the GNAT superfamily members to acquire various specificities. The yeast enzymes involved in UDP-GlcNAc biosynthesis are potential targets for antifungal agents. GNA1, a novel member of the Gcn5-related N-acetyltransferase (GNAT) superfamily, participates in UDP-GlcNAc biosynthesis by catalyzing the formation of GlcNAc6P from AcCoA and GlcN6P. We have solved three crystal structures corresponding to the apo Saccharomyces cerevisiae GNA1, the GNA1-AcCoA, and the GNA1-CoA-GlcNAc6P complexes and have refined them to 2.4, 1.3, and 1.8 Å resolution, respectively. These structures not only reveal a stable, %-intertwined, dimeric assembly with the GlcNAc6P binding site located at the dimer interface but also shed light on the catalytic machinery of GNA1 at an atomic level. Hence, they broaden our understanding of structural features required for GNAT activity, provide structural details for related aminoglycosideN-acetyltransferases, and highlight the adaptability of the GNAT superfamily members to acquire various specificities. Gcn5-relatedN-acetyltransferase histone acetyltransferase serotonin N-acetyltransferase multi-wavelength anomalous dispersion The Gcn5-related N-acetyltransferases (GNATs)1 represent a large superfamily of functionally diverse enzymes that catalyze the transfer of an acetyl group from AcCoA to the primary amine of a wide range of acceptor substrates (for a review, see Ref. 1Dyda F. Klein D.C. Hickman A.B. Annu. Rev. Biophys. Biomol. Struct. 2000; 29: 81-103Crossref PubMed Scopus (387) Google Scholar). Recently, three-dimensional structural information has become available with the structures of two aminoglycoside N-acetyltransferases fromSerratia marcescens (SmAAT) (2Wolf E. Vassilev A. Makino Y. Sali A. Nakatani Y. Burley S.K. Cell. 1998; 94: 439-449Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar) and Enterococcus faecium (EfAAT) (3Wybenga-Groot L.E. Draker K. Wright G.D. Berghuis A.M. Struct. Fold. Des. 1999; 7: 497-507Abstract Full Text Full Text PDF Scopus (125) Google Scholar); five histone acetyltransferases (HATs): PCAF (4Clements A. Rojas J.R. Trievel R.C. Wang L. Berger S.L. Marmorstein R. EMBO J. 1999; 18: 3521-3532Crossref PubMed Scopus (140) Google Scholar), HAT1 (5Dutnall R.N. Tafrov S.T. Sternglanz R. Ramakrishnan V. Cell. 1998; 94: 427-438Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar), Tetrahymena GCN5 (tGCN5) (6Lin Y. Fletcher C.M. Zhou J. Allis C.D. Wagner G. Nature. 1999; 400: 86-89Crossref PubMed Scopus (91) Google Scholar, 7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar), yeast GCN5 (yGCN5) (8Trievel R.C. Rojas J.R. Sterner D.E. Venkataramani R.N. Wang L. Zhou J. Allis C.D. Berger S.L. Marmorstein R. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 8931-8936Crossref PubMed Scopus (161) Google Scholar), and Hpa2 (9Angus-Hill M.L. Dutnall R.N. Tafrov S.T. Sternglanz R. Ramakrishnan V. J. Mol. Biol. 1999; 294: 1311-1325Crossref PubMed Scopus (101) Google Scholar); and one arylalkylamineN-acetyltransferase, the serotoninN-acetyltransferase (AANAT) (10Hickman A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). These structures have revealed a structurally conserved GNAT core that is largely involved in AcCoA binding and incorporates elements from the four conserved sequence motifs (A to D) initially identified by sequence analysis (11Sternglanz R. Schindelin H. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 8807-8808Crossref PubMed Scopus (31) Google Scholar,12Neuwald A.F. Landsman D. Trends Biochem. Sci. 1997; 22: 154-155Abstract Full Text PDF PubMed Scopus (390) Google Scholar). Although the GNAT AcCoA binding site is well documented, the binding site of the acceptor substrate has been characterized in only two cases: the histone binding site in the tGCN5-CoA-H3 peptide complex structure (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar) and the serotonin binding site in the AANAT-bisubstrate analog complex structure (10Hickman A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). These two structures also provide the first glances into the catalytic machinery of GNAT. Yet, a better understanding of the diverse modes of acceptor substrate recognition and the catalytic mechanism of the GNATs as well as further insights into the evolution of this superfamily still await additional structural studies of GNAT-substrate complexes. Glucosamine-6-phosphate N-acetyltransferase 1 (GNA1) is a novel amino-sugar N-acetyltransferase member of the GNAT superfamily. GNA1 holds a key position in the pathway toward de novo synthesis of the essential metabolite UDP-GlcNAc and is present in various eukaryotic organisms (Fig. 1 A). The GNA1 murine homologue, EMeg32, which possesses an extra 31-residue NH2-terminal region compared with the yeast homologues, has recently been characterized (13Boehmelt G. Fialka I. Brothers G. McGinley M.D. Patterson S.D. Mo R. Hui C.C. Chung S. Huber L.A. Mak T.W. Iscove N.N. J. Biol. Chem. 2000; 275: 12821-12832Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). EMeg32 is essential for embryonic development, and its inactivation in mouse embryonic fibroblasts generates resistance to apoptotic stimuli and defects in cell proliferation (14Boehmelt G. Wakeham A. Elia A. Sasaki T. Plyte S. Potter J. Yang Y. Tsang E. Ruland J. Iscove N.N. Dennis J.W. Mak T.W. EMBO J. 2000; 19: 5092-5104Crossref PubMed Scopus (134) Google Scholar). GNA1 has also been characterized in yeast (15Mio T. Yamada-Okabe T. Arisawa M. Yamada-Okabe H. J. Biol. Chem. 1999; 274: 424-429Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar) and shown to be essential to the survival of Saccharomyces cerevisiae in which it controls multiple cell cycle steps (16Lin R. Allis C.D. Elledge S.J. Genes Cells. 1996; 1: 923-942Crossref PubMed Scopus (19) Google Scholar). In addition, Candida albicans GNA1 null mutants exhibit reduced virulence when injected into mice (17Mio T. Kokado M. Arisawa M. Yamada-Okabe H. Microbiology. 2000; 146: 1753-1758Crossref PubMed Scopus (36) Google Scholar), making GNA1 a potential target for the development of new antifungal agents. We present here three high resolution crystal structures of GNA1. The apo GNA1 and the binary GNA1-AcCoA complex structures were solved independently using MAD techniques and refined to 2.4 and 1.3 Å resolution, respectively (Table I). The structure of the GNA1-CoA-GlcNAc6P ternary complex was solved by molecular replacement and refined to 1.8 Å resolution (TableI). These three structures reveal GNA1 catalytic features and provide the first complete picture of an amino-sugar GNAT active site as a first step toward the development of specific inhibitors.Table IStructural statisticsf′′ maximumf′ minimumRemoteHigh resolution1-aNumbers in parentheses refer to values for the highest resolution shell.ApoAcCoAApoAcCoAApoAcCoAApoAcCoACoA-GlcNAc6PData collectionBeamlineID14-4ID14-4ID14-4ID14-4ID14-2DESY − X31λ (Å)0.97940.98020.93240.93240.93261.1000Resolution (Å)20–3.230–3.220–3.230–3.220–3.230–3.230–2.430–1.330–1.8Rsym1-bRsym = Σ‖I − 〈I〉‖/ΣI, whereI is intensity and 〈I〉 is the averageI for all equivalent reflections.(%)5.54.45.64.74.75.17.8 (13.5)4.5 (37.6)4.8 (41.2)Ranom1-cRanom = Σ‖〈I +〉 − 〈I〉‖/Σ(‖〈I +〉 + 〈I〉‖), where I + andI − are the intensities of Bijvoet positive and negative reflections, respectively.(%)6.06.24.54.04.65.1I/ς (I)8.711.97.47.49.711.96.1 (4.7)8.0 (1.9)12.5 (1.8)Completeness (%)99.399.099.699.399.699.393.8 (91.6)96.6 (92.3)97.4 (96.3)Anomalous completeness94.793.094.996.795.196.4Refinement statisticsApoAcCoACoA-GlcNAc6PResolution range (Å)25–2.420–1.325–1.8Rwork/Rfree(%)22.1/28.721.0/22.118.4/22.3Total reflections1-dValues in parentheses refer to the number of reflections used in the random test set.37865 (1887)163364 (2954)62747 (1123)Total atoms (protein/ligands/solvent)7418/0/2744922/204/6415034/150/539Mean B factors (Å2)Main chain/side chain31.2/33.115.0/18.524.0/27.5Solvent/ligand32.5/027.5/17.337.1/25.1r.m.s.d.1-er.m.s.d., root mean square deviation.of bonds (Å)0.0140.0180.019r.m.s.d. of angles/dihedrals/impropers (°)1.8/24.4/1.01.6/23.1/1.21.8/23.6/1.11-a Numbers in parentheses refer to values for the highest resolution shell.1-b Rsym = Σ‖I − 〈I〉‖/ΣI, whereI is intensity and 〈I〉 is the averageI for all equivalent reflections.1-c Ranom = Σ‖〈I +〉 − 〈I〉‖/Σ(‖〈I +〉 + 〈I〉‖), where I + andI − are the intensities of Bijvoet positive and negative reflections, respectively.1-d Values in parentheses refer to the number of reflections used in the random test set.1-e r.m.s.d., root mean square deviation. Open table in a new tab Full-length GNA1 was amplified from genomic S. cerevisiae DNA, cloned into the pQE30 expression vector, and transformed into M15pREP4 (Qiagen) Escherichia coli cells. Protein expression was induced with 0.1 mmisopropyl-1-thio-%-d-galactopyranoside for 20 h at 37 °C. Selenomethionyl GNA1 was produced as previously published (18Van Duyne G.D. Standaert R.F. Karplus P.A. Schreiber S.L. Clardy J. J. Mol. Biol. 1993; 229: 105-124Crossref PubMed Scopus (1099) Google Scholar). The recombinant His-tagged native and selenomethionyl enzymes were purified via nickel affinity and anion exchange chromatographies, dialyzed against 10 mm Tris-HCl, pH 8, 150 mm NaCl, 1 mm dithiothreitol, and concentrated to 10 mg/ml. The activity of these enzymes was verified. Crystals of the native and selenomethionyl protein were grown at 20 °C using the hanging-drop vapor diffusion method by mixing equal volumes of the protein solution and the reservoir, which contained 17–22% polyethylene glycol 600 and 0.2/0.4m imidazole/malate, pH 5.1. Crystals obtained from the apo protein belong to the orthorhombic space group P212121 and contain 6 molecules/asymmetric unit. Those obtained from GNA1 preincubated overnight with 1 mm AcCoA or CoA belong to the monoclinic space group C2 and contain 4 molecules/asymmetric unit. For data collection, the crystals were transferred to a reservoir solution containing 32% polyethylene glycol 600 and flash-frozen at 100 K in gaseous nitrogen. A three-wavelength MAD experiment was performed at the ESRF beamline ID14-4 (European Synchroton on the and apo selenomethionyl protein crystals at and Å resolution, respectively. resolution data were at 2.4 and 1.3 Å resolution on an apo GNA1 crystal and a GNA1-AcCoA complex on beamline A 1.8 Å resolution data was at from a complex crystal in the reservoir solution with 1 mm GlcNAc6P for 6 data were and reduced using in Scholar) and the Biol. Scholar). The apo and GNA1 structures were solved independently using J. Biol. 1999; PubMed Scopus Google Scholar). The MAD were by and with the Biol. Scholar). The apo GNA1 was using A. Scholar). The GNA1-AcCoA complex was using A. R. Struct. Biol. 1999; PubMed Scopus Google Scholar). These two were refined against high resolution data using the J. M. T. Biol. 1998; PubMed Scopus Google Scholar), and were used only for the apo GNA1 factors and are with to in the two The of the apo GNA1 have an root mean square of Å for all In the GNA1-AcCoA complex the root mean square the is Å for all The GNA1-CoA-GlcNAc6P complex structure was obtained from a using the GNA1-AcCoA complex as a revealed the of the CoA and GlcNAc6P in two of the four The structure of the complex was also solved at of the two ternary complexes and revealed that and GlcNAc6P were the GNA1-CoA-GlcNAc6P structure was obtained at a resolution that of only in the analysis the GNA1-CoA-GlcNAc6P complex The of the refined was by R. M. D. J. J. 1993; Google Scholar); was in the of the The of and GNA1 have been in the Protein and and were with The for Scholar) and Biol. PubMed Scopus Google Scholar) for 1 which was with Protein 1993; PubMed Scopus Google Scholar). The three-dimensional structures of GNA1 in its apo and with AcCoA or with CoA and GlcNAc6P have been solved and refined at 2.4, 1.3, and 1.8 Å resolution, respectively. the is well for these structures (Fig. 1 for a to from sequence GNA1 structural with GNAT superfamily members F. Klein D.C. Hickman A.B. Annu. Rev. Biophys. Biomol. Struct. 2000; 29: 81-103Crossref PubMed Scopus (387) Google Scholar, R. Schindelin H. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 8807-8808Crossref PubMed Scopus (31) Google Scholar). The GNA1 of a of a by 4 and a which is from the core A). The GNA1 structure is dimeric in the crystal as well as in as from data The dimer is of two GNA1 in which of one with the from the (Fig. A). A exchange in a dimer is an GNATs and has been only in the Hpa2 structure (9Angus-Hill M.L. Dutnall R.N. Tafrov S.T. Sternglanz R. Ramakrishnan V. J. Mol. Biol. 1999; 294: 1311-1325Crossref PubMed Scopus (101) Google Scholar). In all structurally characterized that a (5Dutnall R.N. Tafrov S.T. Sternglanz R. Ramakrishnan V. Cell. 1998; 94: 427-438Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar), the its is of three-dimensional in which the that the from a to an to a or a dimeric D. Protein Chem. 1997; PubMed Google Scholar). In the of GNA1 or the is to a and the dimeric assembly is further by a two features that three-dimensional the GNATs and the of GNA1 and Hpa2 are related by evolution from a and the that have to dimer formation have three-dimensional In of the GNA1 AcCoA is in a large located at the site where the two and of a in that the of and on the of the The of this is well conserved which a for this structural in the formation of the AcCoA binding AcCoA a to that in GNAT structures F. Klein D.C. Hickman A.B. Annu. Rev. Biophys. Biomol. Struct. 2000; 29: 81-103Crossref PubMed Scopus (387) Google Scholar). The acetyl group of which the active is located and the and is largely by with the the two atoms with and and the into an by the of and an has been in the structurally K. S. E. G. Struct. Biol. 1998; PubMed Scopus Google Scholar) but is a the structurally characterized of the apo and GNA1 structures that AcCoA binding structural that are to the of the and in a in the and in the the of by and toward the of the (Fig. A). these induced are a for acceptor substrate binding as shown for GNATs J. J. Klein D.C. P.A. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, Vassilev A. L.A. Nakatani Y. P.A. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, Y. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus (125) Google Scholar) to be by A with GNATs that these from for in which the AcCoA binding to the histone (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar); and in which a of the region AcCoA binding to complete the serotonin binding site (10Hickman A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). the binding of AcCoA is it that to the specific binding of the acceptor The GNA1 amino-sugar binding site an as it is at the dimer interface and from the two features only in a structures as that of L. S. F. A. A. L. J. Mol. Biol. 1999; PubMed Scopus Google Scholar). GlcNAc6P at the of the AcCoA a that is with for a of that the group the GlcNAc6P acetyl group is to the acetyl group in the GNA1-AcCoA complex structure (Fig. The via with a as that and the of the (Fig. of the structures of the (2Wolf E. Vassilev A. Makino Y. Sali A. Nakatani Y. Burley S.K. Cell. 1998; 94: 439-449Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar) or (3Wybenga-Groot L.E. Draker K. Wright G.D. Berghuis A.M. Struct. Fold. Des. 1999; 7: 497-507Abstract Full Text Full Text PDF Scopus (125) Google Scholar) two structurally characterized aminoglycoside on that of the GNA1-CoA-GlcNAc6P complex that and GNA1 are an that a for these an aminoglycoside recognition of on that as a that as a in a mechanism the formation of a S. J. Biochem. PubMed Scopus Google Scholar, M. M. Biochem. B Biochem. Mol. Biol. 1998; PubMed Scopus Google Scholar). In structural and data available for GNATs a mechanism a of acceptor substrate on AcCoA F. Klein D.C. Hickman A.B. Annu. Rev. Biophys. Biomol. Struct. 2000; 29: 81-103Crossref PubMed Scopus (387) Google Scholar, Vassilev A. L.A. Nakatani Y. P.A. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, Y. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus (125) Google Scholar). In the GNA1-AcCoA complex the to the AcCoA acetyl group Å to a in acetyl is in the of the acetyl which the formation of an and the of a mechanism as for with this is the position of the group of the GlcNAc6P to that of the substrate which is to a at the AcCoA In addition, the of the amine is by the it with the of (Fig. The AcCoA is via bonds to the of and located in the a that the and the negative on the of the the which of the AcCoA to the anion of the CoA also with the acetyl a in the acetyl group for the A of in is by data (15Mio T. Yamada-Okabe T. Arisawa M. Yamada-Okabe H. J. Biol. Chem. 1999; 274: 424-429Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar). A of the active site of GNA1 also two structural and with members of the GNAT superfamily. The first the GNA1 when compared with the in GNAT a The GNAT is an of the structure in which two on one are a on the Protein Chem. PubMed Scopus Google Scholar). a is when two in a or toward the of the the of a In GNA1, the of and are toward the active site and the the of and toward In all members of the GNAT superfamily in which a the (3Wybenga-Groot L.E. Draker K. Wright G.D. Berghuis A.M. Struct. Fold. Des. 1999; 7: 497-507Abstract Full Text Full Text PDF Scopus (125) Google the is the is the two are toward an with the of the two are into the active site These two have been to a in acceptor substrate binding in (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar) and in the of catalytic in (10Hickman A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar); this in to a in the binding the also catalytic The the of the acceptor substrate group to the In the of and a of well or the acceptor substrate group to the catalytic or was to be involved in this (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar, A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). In the GNA1-CoA-GlcNAc6P a is to in which the a position as that of and the not the GNA1 activity (15Mio T. Yamada-Okabe T. Arisawa M. Yamada-Okabe H. J. Biol. Chem. 1999; 274: 424-429Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar), that not as the to the not be in the of GNA1, the of is that of GNAT acceptor substrates as or serotonin is also by the that the pH of purified N-acetyltransferases in the range S. J. Biochem. PubMed Scopus Google Scholar, M. M. Biochem. B Biochem. Mol. Biol. 1998; PubMed Scopus Google Scholar) and by the cerevisiae GNA1 for at pH at pH (13Boehmelt G. Fialka I. Brothers G. McGinley M.D. Patterson S.D. Mo R. Hui C.C. Chung S. Huber L.A. Mak T.W. Iscove N.N. J. Biol. Chem. 2000; 275: 12821-12832Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar), that GNA1 the of GlcN6P. Although the GNAT enzymes structural they have acceptor with in various A analysis of the complexes of tGCN5-CoA-H3 peptide (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar), and AANAT-bisubstrate analog (7Rojas J.R. Trievel R.C. Zhou J. Mo Y. Li X. Berger S.L. Allis C.D. Marmorstein R. Nature. 1999; 401: 93-98Crossref PubMed Scopus (235) Google Scholar, A.B. Namboodiri M.A. Klein D.C. Dyda F. Cell. 1999; 97: 361-369Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar) the structural for the substrate this is essential for the of specific for The structural of these three complexes that the and the GNAT structures and are for substrate The NH2-terminal structural the region and are in the In the toward the active site as it on its with the the active the binding of a substrate A). In the and to one of the substrate binding specific binding for the histone (Fig. In GNA1, the not in acceptor substrate but it to and exchange with the of the in the of using this GNA1 its to specific an of the GNA1 active site of from the in the dimer (Fig. In this region is in by a and which largely to one of the serotonin binding site (Fig. A). For the the to the active site to a (Fig. GNA1 was shown to multiple cell cycle steps in S. cerevisiae (16Lin R. Allis C.D. Elledge S.J. Genes Cells. 1996; 1: 923-942Crossref PubMed Scopus (19) Google Scholar). is still this is related to the N-acetyltransferase activity of GNA1 in UDP-GlcNAc biosynthesis a UDP-GlcNAc and cell cycle or it is the of an additional of GNA1. The of an additional activity for GNA1 was but activity be in T. Yamada-Okabe T. Arisawa M. Yamada-Okabe H. J. Biol. Chem. 1999; 274: 424-429Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar). a of GNA1 with the related GNAT structures that the structural of GNA1 is the which also an dimeric structure (9Angus-Hill M.L. Dutnall R.N. Tafrov S.T. Sternglanz R. Ramakrishnan V. J. Mol. Biol. 1999; 294: 1311-1325Crossref PubMed Scopus (101) Google Scholar). of the two structures in the of the two in acceptor substrate binding A in which the histone is in the Hpa2 structure of the of GNA1, which to an and histone GNA1 an additional via the with a cell or with a protein with the of has been for EMeg32 GNA1 murine which also with the protein (13Boehmelt G. Fialka I. Brothers G. McGinley M.D. Patterson S.D. Mo R. Hui C.C. Chung S. Huber L.A. Mak T.W. Iscove N.N. J. Biol. Chem. 2000; 275: 12821-12832Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). performed in S. cerevisiae revealed GNA1 and a or L. G. J.R. D. V. M. A. Li Y. D. T. G. Yang M. M. S. Nature. 2000; PubMed Scopus Google Scholar). are to the of these UDP-GlcNAc is a key of of the yeast and cell as well as of the of and is essential to and of involved in as the yeast which UDP-GlcNAc as a have been to a in the cell cycle M.A. K. Biophys. 1999; PubMed Scopus (31) Google Scholar). In addition, a that UDP-GlcNAc cell cycle and (14Boehmelt G. Wakeham A. Elia A. Sasaki T. Plyte S. Potter J. Yang Y. Tsang E. Ruland J. Iscove N.N. Dennis J.W. Mak T.W. EMBO J. 2000; 19: 5092-5104Crossref PubMed Scopus (134) Google Scholar). Hence, the of GNA1 in cell cycle to be to its key N-acetyltransferase activity in de novo UDP-GlcNAc The structural data here have to a catalytic mechanism for GNA1, as well as a structural for GNA1 and related these further the of the GNAT superfamily and represent a step toward the development of specific We and for for and the ESRF for in data
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