scholarly journals Structure of the Q67H mutant of R67 dihydrofolate reductase-NADP+complex reveals a novel cofactor binding mode

2007 ◽  
Vol 16 (6) ◽  
pp. 1063-1068 ◽  
Author(s):  
N. Divya ◽  
E. Grifith ◽  
Narendra Narayana
Keyword(s):  
Dihydrofolate Reductase ◽  
Binding Mode ◽  
Cofactor Binding ◽  
R67 Dihydrofolate Reductase

Role of Ionic Interactions in Ligand Binding and Catalysis of R67 Dihydrofolate Reductase†

Biochemistry ◽  
2003 ◽  
Vol 42 (36) ◽  
pp. 10569-10578 ◽  
Author(s):  
Stephanie N. Hicks ◽  
R. Derike Smiley ◽  
J. Bradley Hamilton ◽  
Elizabeth E. Howell
Keyword(s):  
Ligand Binding ◽  
Dihydrofolate Reductase ◽  
Ionic Interactions ◽  
R67 Dihydrofolate Reductase

Does R67 Dihydrofolate Reductase Possess a Proton Donor?

1993 ◽  
pp. 493-498 ◽  
Author(s):  
Janel C. Holland ◽  
Charles E. Linn ◽  
Enrico DiGiammarino ◽  
Robert Nichols ◽  
Elizabeth E. Howell
Keyword(s):  
Dihydrofolate Reductase ◽  
Proton Donor ◽  
R67 Dihydrofolate Reductase

scholarly journals Role of Lys-32 Residues in R67 Dihydrofolate Reductase Probed by Asymmetric Mutations

2004 ◽  
Vol 279 (45) ◽  
pp. 46995-47002 ◽  
Author(s):  
Stephanie N. Hicks ◽  
R. Derike Smiley ◽  
Lori G. Stinnett ◽  
Kenneth H. Minor ◽  
Elizabeth E. Howell
Keyword(s):  
Dihydrofolate Reductase ◽  
R67 Dihydrofolate Reductase

Structural insights into the interaction of p97 N-terminus domain and VBM in rhomboid protease, RHBDL4

2016 ◽  
Vol 473 (18) ◽  
pp. 2863-2880 ◽  
Author(s):  
Jia Jia Lim ◽  
Youngjin Lee ◽  
Tue Tu Ly ◽  
Jung Youn Kang ◽  
Jung-Gyu Lee ◽  
...  
Keyword(s):  
Complex Structure ◽  
Specific Interaction ◽  
Adaptor Proteins ◽  
Binding Mode ◽  
Binding Motif ◽  
Rhomboid Protease ◽  
Cofactor Binding ◽  
Arginine Residues ◽  
Biochemical Analyses ◽  
Structural Insights

RHBDL4 is an active rhomboid that specifically recognizes and cleaves atypical, positively charged transmembrane endoplasmic reticulum-associated degradation (ERAD) substrates. Interaction of valosin-containing protein (p97/VCP) and RHBDL4 is crucial to retrotranslocate polyubiquitinated substrates for ERAD pathway. Here, we report the first complex structure of VCP-binding motif (VBM) with p97 N-terminal domain (p97N) at 1.88 Å resolution. Consistent with p97 adaptor proteins including p47-ubiquitin regulatory X (UBX), gp78-VCP-interacting motif (VIM), OTU1-UBX-like element, and FAF1-UBX, RHBDL4 VBM also binds at the interface between the two lobes of p97N. Notably, the RF residues in VBM are involved in the interaction with p97N, showing a similar interaction pattern with that of FPR signature motif in the UBX domain, although the directionality is opposite. Comparison of VBM interaction with VIM of gp78, another α-helical motif that interacts with p97N, revealed that the helix direction is inversed. Nevertheless, the conserved arginine residues in both motifs participate in the majority of the interface via extensive hydrogen bonds and ionic interactions with p97N. We identified novel VBM-binding mode to p97N that involves a combination of two types of p97–cofactor specificities observed in the UBX and VIM interactions. This highlights the induced fit model of p97N interdomain cleft upon cofactor binding to form stable p97–cofactor complexes. Our mutational and biochemical analyses in defining the specific interaction between VBM and p97N have elucidated the importance of the highly conserved VBM, applicable to other VBM-containing proteins. We also showed that RHBDL4, ubiquitins, and p97 co-operate for efficient substrate dislocation.

Further Studies on the Role of Water in R67 Dihydrofolate Reductase

Biochemistry ◽  
2013 ◽  
Vol 52 (12) ◽  
pp. 2118-2127 ◽  
Author(s):  
Mary Jane Timson ◽  
Michael R. Duff ◽  
Greyson Dickey ◽  
Arnold M. Saxton ◽  
José I. Reyes-De-Corcuera ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
R67 Dihydrofolate Reductase

Effects of Single-Tryptophan Mutations on R67 Dihydrofolate Reductase†

Biochemistry ◽  
2000 ◽  
Vol 39 (13) ◽  
pp. 3678-3689 ◽  
Author(s):  
Freddie W. West ◽  
Han-Seok Seo ◽  
Thomas D. Bradrick ◽  
Elizabeth E. Howell
Keyword(s):  
Dihydrofolate Reductase ◽  
R67 Dihydrofolate Reductase

scholarly journals Redesigning the Quaternary Structure of R67 Dihydrofolate Reductase

1996 ◽  
Vol 271 (45) ◽  
pp. 28031-28037 ◽  
Author(s):  
Thomas D. Bradrick ◽  
Chris Shattuck ◽  
Michael B. Strader ◽  
Carol Wicker ◽  
Edward Eisenstein ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Quaternary Structure ◽  
R67 Dihydrofolate Reductase
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