Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase

2013 ◽  
Vol 125 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Benedikt Kretner ◽  
Akio Fukumori ◽  
Peer-Hendrik Kuhn ◽  
Blanca Isabel Pérez-Revuelta ◽  
Stefan F. Lichtenthaler ◽  
...  
Keyword(s):  
Active Site ◽  
Functional Role ◽  
Substrate Selectivity ◽  
Cleavage Specificity ◽  
Active Site Motif ◽  
Substrate Cleavage

Functional Role of the Active Site Glutamate-368 in Rat Short Chain Acyl-CoA Dehydrogenase†

Biochemistry ◽  
1996 ◽  
Vol 35 (48) ◽  
pp. 15356-15363 ◽  
Author(s):  
Kevin P. Battaile ◽  
Al-Walid A. Mohsen ◽  
Jerry Vockley
Keyword(s):  
Active Site ◽  
Functional Role ◽  
Short Chain ◽  
Chain Acyl

scholarly journals Understanding the Role of Histidine in the GHSxG Acyltransferase Active Site Motif: Evidence for Histidine Stabilization of the Malonyl-Enzyme Intermediate

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109421 ◽  
Author(s):  
Sean Poust ◽  
Isu Yoon ◽  
Paul D. Adams ◽  
Leonard Katz ◽  
Christopher J. Petzold ◽  
...  
Keyword(s):  
Active Site ◽  
Active Site Motif ◽  
Enzyme Intermediate

Functional Role of the Conserved Active Site Proline of Triosephosphate Isomerase†,‡

Biochemistry ◽  
2006 ◽  
Vol 45 (51) ◽  
pp. 15483-15494 ◽  
Author(s):  
Marco G. Casteleijn ◽  
Markus Alahuhta ◽  
Katrin Groebel ◽  
Ibrahim El-Sayed ◽  
Koen Augustyns ◽  
...  
Keyword(s):  
Active Site ◽  
Functional Role ◽  
Triosephosphate Isomerase

scholarly journals Expression, purification, crystallization and preliminary X-ray diffraction analysis of acylpeptide hydrolase fromDeinococcus radiodurans

2014 ◽  
Vol 70 (9) ◽  
pp. 1292-1295 ◽  
Author(s):  
Venkata Narayana Are ◽  
Biplab Ghosh ◽  
Ashwani Kumar ◽  
Pooja Yadav ◽  
Deepak Bhatnagar ◽  
...  
Keyword(s):  
Active Site ◽  
Mammalian Cells ◽  
Deinococcus Radiodurans ◽  
Structural Information ◽  
Screening Method ◽  
Substrate Selectivity ◽  
Cell Parameters ◽  
Acylpeptide Hydrolase ◽  
Monomeric Structure

Acylpeptide hydrolase (APH; EC 3.4.19.1), which belongs to the S9 family of serine peptidases (MEROPS), catalyzes the removal of anN-acylated amino acid from a blocked peptide. The role of this enzyme in mammalian cells has been suggested to be in the clearance of oxidatively damaged proteins as well as in the degradation of the β-amyloid peptides implicated in Alzheimer's disease. Detailed structural information for the enzyme has been reported from two thermophilic archaea; both of the archaeal APHs share a similar monomeric structure. However, the mechanisms of substrate selectivity and active-site accessibility are totally different and are determined by inter-domain flexibility or the oligomeric structure. An APH homologue from a bacterium,Deinococcus radiodurans(APHdr), has been crystallized using microbatch-under-oil employing the random microseed matrix screening method. The protein crystallized in space groupP21, with unit-cell parametersa= 77.6,b= 189.6,c= 120.4 Å, β = 108.4°. A Matthews coefficient of 2.89 Å3 Da−1corresponds to four monomers, each with a molecular mass of ∼73 kDa, in the asymmetric unit. The APHdr structure will reveal the mechanisms of substrate selectivity and active-site accessibility in the bacterial enzyme. It will also be helpful in elucidating the functional role of this enzyme inD. radiodurans.

scholarly journals Shaping Substrate Selectivity in a Broad-Spectrum Metallo-β-Lactamase

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Lisandro J. González ◽  
Cintia Stival ◽  
Juan L. Puzzolo ◽  
Diego M. Moreno ◽  
Alejandro J. Vila
Keyword(s):  
Broad Spectrum ◽  
Active Site ◽  
Substrate Recognition ◽  
Chimeric Protein ◽  
Major Group ◽  
Substrate Selectivity ◽  
Incomplete Knowledge ◽  
Naturally Occurring ◽  
The One

ABSTRACTMetallo-β-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited by, among other issues, incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a chimeric protein in which the sequence insertion of SPM-1 was replaced by the one present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing that the substrate profile of MBLs can be further tuned depending on the protein context. These results also show that the stable scaffold of MBLs allows a modular engineering much richer than the one observed in nature.

Probing the Functional Role of Two Conserved Active Site Aspartates in Mouse Adenosine Deaminase†

Biochemistry ◽  
1996 ◽  
Vol 35 (24) ◽  
pp. 7862-7872 ◽  
Author(s):  
Vera Sideraki ◽  
Khalid A. Mohamedali ◽  
David K. Wilson ◽  
Zengyi Chang ◽  
Rodney E. Kellems ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Active Site ◽  
Functional Role
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