Alteration of the quaternary structure of human UDP-glucose dehydrogenase by a double mutation.
There are conflicting views for the polymerization process of human UDP-glucose dehydrogenase (UGDH) and no clear evidence has been reported yet. Based on crystal coordinates for Streptococcus pyogenes UGDH, we made double mutant A222Q/S233G. The double mutagenesis had no effects on expression, stability, and secondary structure. Interestingly, A222Q/S233G was a dimeric form and showed an UGDH activity, although it showed increased Km values for substrates. These results suggest that Ala222 and Ser233 play an important role in maintaining the hexameric structure and the reduced binding affinities for substrates are attributable to its altered subunit communication although quaternary structure may not be critical for catalysis.
Huh
Jae-Wan
JW
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Yang
Seung-Ju
SJ
Hwang
Eun Young
EY
Choi
Myung-Min
MM
Lee
Hyun-Ju
HJ
Kim
Eun-A
EA
Choi
Soo Young
SY
Choi
Jene
J
Hong
Hea-Nam
HN
Cho
Sung-Woo
SW
D000409:Alanine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D009154:Mutation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D012694:Serine; D014533:Uridine Diphosphate Glucose Dehydrogenase; D000409:Alanine