scholarly journals An Exon Splice Enhancer Primes IGF2:IGF2R Binding Site Structure and Function Evolution

Science ◽  
2012 ◽  
Vol 338 (6111) ◽  
pp. 1209-1213 ◽  
Author(s):  
C. Williams ◽  
H.-J. Hoppe ◽  
D. Rezgui ◽  
M. Strickland ◽  
B. E. Forbes ◽  
...  
Keyword(s):  
Binding Site ◽  
Structure And Function ◽  
Splice Enhancer ◽  
Site Structure ◽  
Exon Splice ◽  
And Function

Metalloenzyme Active-Site Structure and Function through Multifrequency CW and Pulsed ENDOR

1993 ◽  
pp. 151-218 ◽  
Author(s):  
Brian M. Hoffman ◽  
Victoria J. DeRose ◽  
Peter E. Doan ◽  
Ryszard J. Gurbiel ◽  
Andrew L. P. Houseman ◽  
...  
Keyword(s):  
Active Site ◽  
Structure And Function ◽  
Site Structure ◽  
Active Site Structure ◽  
And Function

scholarly journals Structural Characterization of Carbonic Anhydrase VIII and Effects of Missense Single Nucleotide Variations to Protein Structure and Function

2020 ◽  
Vol 21 (8) ◽  
pp. 2764
Author(s):  
Taremekedzwa Allan Sanyanga ◽  
Özlem Tastan Bishop
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Site ◽  
Cross Correlation ◽  
Structure And Function ◽  
The Body ◽  
Conformational Sampling ◽  
Nucleotide Polymorphisms ◽  
Ip3 Receptor ◽  
Single Nucleotide ◽  
And Function

Human carbonic anhydrase 8 (CA-VIII) is an acatalytic isoform of the α -CA family. Though the protein cannot hydrate CO2, CA-VIII is essential for calcium (Ca2+) homeostasis within the body, and achieves this by allosterically inhibiting the binding of inositol 1,4,5-triphosphate (IP3) to the IP3 receptor type 1 (ITPR1) protein. However, the mechanism of interaction of CA-VIII to ITPR1 is not well understood. In addition, functional defects to CA-VIII due to non-synonymous single nucleotide polymorphisms (nsSNVs) result in Ca2+ dysregulation and the development of the phenotypes such as cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (CAMRQ3). The pathogenesis of CAMRQ3 is also not well understood. The structure and function of CA-VIII was characterised, and pathogenesis of CAMRQ3 investigated. Structural and functional characterisation of CA-VIII was conducted through SiteMap and CPORT to identify potential binding site residues. The effects of four pathogenic nsSNVs, S100A, S100P, G162R and R237Q, and two benign S100L and E109D variants on CA-VIII structure and function was then investigated using molecular dynamics (MD) simulations, dynamic cross correlation (DCC) and dynamic residue network (DRN) analysis. SiteMap and CPORT analyses identified 38 unique CA-VIII residues that could potentially bind to ITPR1. MD analysis revealed less conformational sampling within the variant proteins and highlighted potential increases to variant protein rigidity. Dynamic cross correlation (DCC) showed that wild-type (WT) protein residue motion is predominately anti-correlated, with variant proteins showing no correlation to greater residue correlation. DRN revealed variant-associated increases to the accessibility of the N-terminal binding site residues, which could have implications for associations with ITPR1, and further highlighted differences to the mechanism of benign and pathogenic variants. SNV presence is associated with a reduction to the usage of Trp37 in all variants, which has implications for CA-VIII stability. The differences to variant mechanisms can be further investigated to understand pathogenesis of CAMRQ3, enhancing precision medicine-related studies into CA-VIII.

Structure and Function of the Xenobiotic Substrate-Binding Site and Location of a Potential Non-Substrate-Binding Site in a Class π GlutathioneS-Transferase†,‡

Biochemistry ◽  
1997 ◽  
Vol 36 (32) ◽  
pp. 9690-9702 ◽  
Author(s):  
Xinhua Ji ◽  
Maria Tordova ◽  
Rosemary O'Donnell ◽  
James F. Parsons ◽  
Janet B. Hayden ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Structure And Function ◽  
Substrate Binding Site ◽  
And Function

Insight into the active-site structure and function of cytochrome oxidase by analysis of site-directed mutants of bacterial cytochromeaa 3 and cytochromebo

1993 ◽  
Vol 25 (2) ◽  
pp. 121-136 ◽  
Author(s):  
Jonathan P. Hosler ◽  
Shelagh Ferguson-Miller ◽  
Melissa W. Calhoun ◽  
Jeffrey W. Thomas ◽  
John Hill ◽  
...  
Keyword(s):  
Cytochrome Oxidase ◽  
Active Site ◽  
Structure And Function ◽  
Site Structure ◽  
Active Site Structure ◽  
And Function ◽  
Insight Into

Structure and Function of Residue 104 and Water Molecules in the Xenobiotic Substrate-Binding Site in Human GlutathioneS-Transferase P1-1†,‡

Biochemistry ◽  
1999 ◽  
Vol 38 (32) ◽  
pp. 10231-10238 ◽  
Author(s):  
Xinhua Ji ◽  
Jaroslaw Blaszczyk ◽  
Bing Xiao ◽  
Rosemary O'Donnell ◽  
Xun Hu ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Structure And Function ◽  
Water Molecules ◽  
Substrate Binding Site ◽  
And Function

scholarly journals Activity and Affinity of Pin1 Variants

2019 ◽  
Author(s):  
Alexandra Born ◽  
Morkos A. Henen ◽  
Beat Vögeli
Keyword(s):  
Catalytic Activity ◽  
Ligand Binding ◽  
Binding Site ◽  
Structure And Function ◽  
Ligand Binding Site ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Isomerase Activity ◽  
Ppiase Domain ◽  
And Function

Pin1 is a peptidyl-prolyl isomerase responsible for isomerizing phosphorylated S/T-P motifs. Pin1 has two domains that each have a distinct ligand binding site, but only its PPIase domain has catalytic activity. Vast evidence supports interdomain allostery of Pin1, with binding of a ligand to its regulatory WW domain impacting activity in the PPIase domain. Many diverse studies have made mutations in Pin1 in order to elucidate interactions that are responsible for ligand binding, isomerase activity, and interdomain allostery. Here, we summarize these mutations and their impact on Pin1’s structure and function.

Sign in / Sign up

Export Citation Format

Share Document