PMID: 8601841Mar 15, 1996Paper

The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer

Journal of Molecular Biology
M KonnoN Takahashi

Abstract

The three-dimensional structure of Escherichia coli cytosolic cyclophilin A (CyPA) complexed with a tripeptide (succinyl-Ala-Pro-Ala-p-nitroanilide) was refined at 1.8 A resolution by the multiple isomorphous replacement method to a crystallographic R-factor of 17.6%. As in human CyPA, the peptide binding site in E. coli enzyme is in a cleft created on the surface of the upper sheet of two orthogonal beta-sheets. In this cleft, the walls of the hydrophobic pocket are formed by the side-chains of five non-polar residues, Phe48, Met49, Phe107, Leu108, and Try120, with Phe99 at the bottom. When the cis isomer of the tripeptide binds to the enzyme, a cis-proline ring is inserted into the hydrophobic pocket. Since the binding pocket of CyPAs are largely hydrophobic, the cis isomer of a peptide can be bound more firmly than the trans isomer. Distortion of the trans isomer could lead to better binding, but at an energetic cost of the distortion energy. At the periphery of the upper beta-sheet in E. coli CyPA, conformations of loops L1, L3, and L4 and the segment connecting alpha1 and beta3 with deletions or insertions against human CyPA differ significantly from those in human CyPA. The refined model also shows that steric hindrance t...Continue Reading

Citations

Jul 9, 1998·Protein Science : a Publication of the Protein Society·V MikolC K Carlow
Mar 24, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Elias ChristoforidesMichael Karpusas
Nov 22, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Aggeliki SkagiaMaria Dimou
Nov 4, 2000·Medicinal Research Reviews·M T Ivery
Oct 30, 2009·Protein Science : a Publication of the Protein Society·Ulrich WeiningerFranz X Schmid
Jan 24, 1998·Nature·E QuéméneurA Ménez
Sep 10, 2004·European Journal of Biochemistry·Michiko KonnoHiroshi Matsuzawa
Jan 17, 2007·European Biophysics Journal : EBJ·Pekka Mark, Lennart Nilsson
Jan 1, 1997·Progress in Biophysics and Molecular Biology·P TaylorM D Walkinshaw
Jun 7, 2018·Bioconjugate Chemistry·Adarshi P WelegedaraGottfried Otting
Oct 25, 2001·The Journal of Organic Chemistry·Scott A. Hart, Felicia A. Etzkorn

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.