Regional assignment of the human gene coding for a multifunctional polypeptide (P4HB) acting as the β-subunit of prolyl 4-hydroxylase and the enzyme protein disulfide isomerase to 17q25

1991 ◽  
Vol 56 (3-4) ◽  
pp. 165-168 ◽  
Author(s):  
L. Pajunen ◽  
T.A. Jones ◽  
A. Goddard ◽  
D. Sheer ◽  
E. Solomon ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Human Gene ◽  
Beta Subunit ◽  
Enzyme Protein ◽  
Disulfide Isomerase ◽  
Gene Coding ◽  
Protein Disulfide ◽  
Regional Assignment

scholarly journals Route Exploration and Synthesis of the Reported Pyridone-Based PDI Inhibitor STK076545

2020 ◽  
Author(s):  
Eric Greve ◽  
Sergey Lindeman ◽  
Chris Dockendorff
Keyword(s):  
Protein Disulfide Isomerase ◽  
Enzyme Protein ◽  
Allyl Ester ◽  
Disulfide Isomerase ◽  
X Ray ◽  
Surface Receptors ◽  
Promising Target ◽  
Biological Studies ◽  
Final Compound ◽  
Protein Disulfide

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported b-keto-amide with an N-alkylated pyridone at the a-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an a-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

scholarly journals A single polypeptide acts both as the beta subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase.

1987 ◽  
Vol 262 (14) ◽  
pp. 6447-6449 ◽  
Author(s):  
J Koivu ◽  
R Myllylä ◽  
T Helaakoski ◽  
T Pihlajaniemi ◽  
K Tasanen ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Beta Subunit ◽  
Disulfide Isomerase ◽  
Single Polypeptide ◽  
Protein Disulfide

Structures of the Human Gene for the Protein Disulfide Isomerase-Related Polypeptide ERp60 and a Processed Gene and Assignment of These Genes to 15q15 and 1q21

Genomics ◽  
1997 ◽  
Vol 42 (3) ◽  
pp. 397-404 ◽  
Author(s):  
Peppi Koivunen ◽  
Nina Horelli-Kuitunen ◽  
Tarja Helaakoski ◽  
Päivi Karvonen ◽  
Marko Jaakkola ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Human Gene ◽  
Disulfide Isomerase ◽  
Protein Disulfide

Platelet protein disulfide isomerase is localized in the dense tubular system and does not become surface expressed after activation

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4738-4740 ◽  
Author(s):  
Hezder E. van Nispen tot Pannerden ◽  
Suzanne M. van Dijk ◽  
Vivian Du ◽  
Harry F. G. Heijnen
Keyword(s):  
Cell Surface ◽  
Protein Disulfide Isomerase ◽  
Active Conformation ◽  
Enzyme Protein ◽  
Disulfide Isomerase ◽  
Anionic Phospholipids ◽  
Platelet Protein ◽  
Activated Platelets ◽  
Tubular System ◽  
Protein Disulfide

Abstract Evidence is accumulating that circulating tissue factor (TF) contributes to the initiation of coagulation and the formation of fibrin. The majority of circulating TF is cryptic, and it has been suggested that close vicinity with anionic phospholipids on the cell surface increases the active conformation of TF. Two recent papers have shown that encryption of TF and initiation of coagulation are facilitated by the enzyme protein disulfide isomerase (PDI), possibly on the surface of activated platelets or endothelial cells. In this brief report, we demonstrate that the majority of PDI in platelets is intracellular where it is exclusively located in the dense tubular system. On activation, PDI remains confined to the intracellular stores of the dense tubular system and is neither released nor targeted to the cell surface. Similar results were obtained in endothelium where PDI remains exclusively localized in the endoplasmic reticulum, both at steady state and after thrombin stimulation.

scholarly journals Route Exploration and Synthesis of the Reported Pyridone-Based PDI Inhibitor STK076545

2020 ◽  
Author(s):  
Eric Greve ◽  
Sergey Lindeman ◽  
Chris Dockendorff
Keyword(s):  
Protein Disulfide Isomerase ◽  
Enzyme Protein ◽  
Allyl Ester ◽  
Disulfide Isomerase ◽  
X Ray ◽  
Surface Receptors ◽  
Promising Target ◽  
Biological Studies ◽  
Final Compound ◽  
Protein Disulfide

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported b-keto-amide with an N-alkylated pyridone at the a-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an a-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

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