3GEG

Fingerprint and Structural Analysis of a SCOR enzyme with its bound cofactor from Clostridium thermocellum

Replaces:  3DIJ

Summary for 3GEG

• Entry DOI: 10.2210/pdb3geg/pdb
• Related: 3GED
• Descriptor: Short-chain dehydrogenase/reductase SDR, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, GLYCEROL, ... (6 entities in total)
• Functional Keywords: sdr, scor, rossmann fold, oxidoreductase
• Biological source: Clostridium thermocellum ATCC 27405
• Total number of polymer chains: 2
• Total formula weight: 56528.13

Authors

Huether, R.,Liu, Z.J.,Xu, H.,Wang, B.C.,Pletnev, V.,Mao, Q.,Umland, T.,Duax, W. (deposition date: 2009-02-25, release date: 2009-03-17, Last modification date: 2023-09-06)

Primary citation

Huether, R.,Liu, Z.J.,Xu, H.,Wang, B.C.,Pletnev, V.Z.,Mao, Q.,Duax, W.L.,Umland, T.C.
Sequence fingerprint and structural analysis of the SCOR enzyme A3DFK9 from Clostridium thermocellum.
Proteins, 78:603-613, 2010

PubMed Abstract: We have identified a highly conserved fingerprint of 40 residues in the TGYK subfamily of the short-chain oxidoreductase enzymes. The TGYK subfamily is defined by the presence of an N-terminal TGxxxGxG motif and a catalytic YxxxK motif. This subfamily contains more than 12,000 members, with individual members displaying unique substrate specificities. The 40 fingerprint residues are critical to catalysis, cofactor binding, protein folding, and oligomerization but are substrate independent. Their conservation provides critical insight into evolution of the folding and function of TGYK enzymes. Substrate specificity is determined by distinct combinations of residues in three flexible loops that make up the substrate-binding pocket. Here, we report the structure determinations of the TGYK enzyme A3DFK9 from Clostridium thermocellum in its apo form and with bound NAD(+) cofactor. The function of this protein is unknown, but our analysis of the substrate-binding loops putatively identifies A3DFK9 as a carbohydrate or polyalcohol metabolizing enzyme. C. thermocellum has potential commercial applications because of its ability to convert biomaterial into ethanol. A3DFK9 contains 31 of the 40 TGYK subfamily fingerprint residues. The most significant variations are the substitution of a cysteine (Cys84) for a highly conserved glycine within a characteristic VNNAG motif, and the substitution of a glycine (Gly106) for a highly conserved asparagine residue at a helical kink. Both of these variations occur at positions typically participating in the formation of a catalytically important proton transfer network. An alternate means of stabilizing this proton wire was observed in the A3DFK9 crystal structures.

PubMed: 19774618
DOI: 10.1002/prot.22584

Experimental method

X-RAY DIFFRACTION (2.102 Å)