3C3E

Crystal structure of 2-phospho-(S)-lactate transferase from Methanosarcina mazei in complex with Fo and GDP. Northeast Structural Genomics Consortium target MaR46

Summary for 3C3E

• Entry DOI: 10.2210/pdb3c3e/pdb
• Related: 3C3D 3CGW
• Descriptor: 2-phospho-L-lactate transferase, 1-deoxy-1-(8-hydroxy-2,4-dioxo-3,4-dihydropyrimido[4,5-b]quinolin-10(2H)-yl)-D-ribitol, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: alpha-beta protein, structural genomics, psi-2, protein structure initiative, northeast structural genomics consortium, nesg, magnesium, transferase
• Biological source: Methanosarcina mazei Go1
• Total number of polymer chains: 4
• Total formula weight: 142579.39

Authors

Forouhar, F.,Abashidze, M.,Xu, H.,Grochowski, L.L.,Seetharaman, J.,Hussain, M.,Kuzin, A.P.,Chen, Y.,Zhou, W.,Xiao, R.,Acton, T.B.,Montelione, G.T.,Galinier, A.,White, R.H.,Tong, L.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2008-01-28, release date: 2008-02-19, Last modification date: 2024-10-16)

Primary citation

Forouhar, F.,Abashidze, M.,Xu, H.,Grochowski, L.L.,Seetharaman, J.,Hussain, M.,Kuzin, A.,Chen, Y.,Zhou, W.,Xiao, R.,Acton, T.B.,Montelione, G.T.,Galinier, A.,White, R.H.,Tong, L.
Molecular insights into the biosynthesis of the f420 coenzyme.
J.Biol.Chem., 283:11832-11840, 2008

PubMed Abstract: Coenzyme F(420), a hydride carrier, is found in Archaea and some bacteria and has crucial roles in methanogenesis, antibiotic biosynthesis, DNA repair, and activation of antitubercular compounds. CofD, 2-phospho-l-lactate transferase, catalyzes the last step in the biosynthesis of F(420)-0 (F(420) without polyglutamate), by transferring the lactyl phosphate moiety of lactyl(2)diphospho-(5')guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin ribitol (Fo). CofD is highly conserved among F(420)-producing organisms, and weak sequence homologs are also found in non-F(420)-producing organisms. This superfamily does not share any recognizable sequence conservation with other proteins. Here we report the first crystal structures of CofD, the free enzyme and two ternary complexes, with Fo and P(i) or with Fo and GDP, from Methanosarcina mazei. The active site is located at the C-terminal end of a Rossmann fold core, and three large insertions make significant contributions to the active site and dimer formation. The observed binding modes of Fo and GDP can explain known biochemical properties of CofD and are also supported by our binding assays. The structures provide significant molecular insights into the biosynthesis of the F(420) coenzyme. Large structural differences in the active site region of the non-F(420)-producing CofD homologs suggest that they catalyze a different biochemical reaction.

PubMed: 18252724
DOI: 10.1074/jbc.M710352200

Experimental method

X-RAY DIFFRACTION (3 Å)