C-Terminal Analogues of Parathyroid Hormone:  Effect of C-Terminus Function on Helical Structure, Stability, and Bioactivity

Biochemistry ◽  
2006 ◽  
Vol 45 (37) ◽  
pp. 11113-11121 ◽  
Author(s):  
Zhanna Potetinova ◽  
Jean-René Barbier ◽  
Tanya Suen ◽  
Thomas Dean ◽  
Thomas J. Gardella ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Helical Structure ◽  
Structure Stability ◽  
C Terminus ◽  
Hormone Effect

scholarly journals Primary- and secondary-structural analysis of a unique prokaryotic metallothionein from a Synechococcus sp. cyanobacterium

1988 ◽  
Vol 251 (3) ◽  
pp. 691-699 ◽  
Author(s):  
R W Olafson ◽  
W D McCubbin ◽  
C M Kay
Keyword(s):  
Amino Acid ◽  
Metal Binding ◽  
Helical Structure ◽  
Basic Amino Acid ◽  
Cysteine Residues ◽  
Amino Acid Residues ◽  
C Terminus ◽  
Empirical Relations ◽  
Heavy Metal Binding ◽  
Synechococcus Sp

Biochemical and physiological studies of Synechococcus cyanobacteria have indicated the presence of a low-Mr heavy-metal-binding protein with marked similarity to eukaryotic metallothioneins (MTs). We report here the characterization of a Synechococcus prokaryotic MT isolated by gel-permeation and reverse-phase chromatography. The large number of variants of this molecule found during chromatographic separation could not be attributed to the presence of major isoproteins as assessed by amino acid analysis and amino acid sequencing of isoforms. Two of the latter were shown to have identical primary structures that differed substantially from the well-described eukaryotic MTs. In addition to six long-chain aliphatic residues, two aromatic residues were found adjacent to one another near the centre of the molecule, making this the most hydrophobic MT to be described. Other unusual features included a pair of histidine residues located in repeating Gly-His-Thr-Gly sequences near the C-terminus and a complete lack of association of hydroxylated residues with cysteine residues, as is commonly found in eukaryotes. Similarly, aside from a single lysine residue, no basic amino acid residues were found adjacent to cysteine residues in the sequence. Most importantly, sequence alignment analyses with mammalian, invertebrate and fungal MT sequences showed no statistically significant homology aside from the presence of Cys-Xaa-Cys structures common to all MTs. On the other hand, like other MTs, the prokaryotic molecule appears to be free of alpha-helical structure but has a considerable amount of beta-structure, as predicted by both c.d. measurements and the Chou & Fasman empirical relations. Considered together, these data suggested that some similarity between the metal-thiolate clusters of the prokaryote and eukaryote MTs may exist.

The role of the C-terminus and Kpn loop in the quaternary structure stability of nucleoside diphosphate kinase from Leishmania parasites

2015 ◽  
Vol 192 (3) ◽  
pp. 336-341 ◽  
Author(s):  
Plínio Salmazo Vieira ◽  
Priscila Oliveira de Giuseppe ◽  
Arthur Henrique Cavalcante de Oliveira ◽  
Mario Tyago Murakami
Keyword(s):  
Quaternary Structure ◽  
Nucleoside Diphosphate Kinase ◽  
Structure Stability ◽  
C Terminus ◽  
Leishmania Parasites

α-Helical structure in the C-terminus of vasoactive intestinal peptide: functional and structural consequences

2004 ◽  
Vol 485 (1-3) ◽  
pp. 307-316 ◽  
Author(s):  
Satomi Onoue ◽  
Asami Matsumoto ◽  
Yumiko Nagano ◽  
Keiichi Ohshima ◽  
Yuki Ohmori ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Helical Structure ◽  
C Terminus

Parathyroid Hormone Effect on the Fragility of Human Young and Old Red Blood Cells in Uremia

Nephron ◽  
1986 ◽  
Vol 42 (1) ◽  
pp. 52-57 ◽  
Author(s):  
T. Malachi ◽  
E. Bogin ◽  
U. Gafter ◽  
J. Levi
Keyword(s):  
Parathyroid Hormone ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Hormone Effect

The C-terminal tetrapeptide HWFW of theChlorellaHUP1 hexose/H+-symporter is essential for full activity and an α-helical structure of the C-terminus

FEBS Letters ◽  
2000 ◽  
Vol 468 (2-3) ◽  
pp. 225-230 ◽  
Author(s):  
Renate Graßl ◽  
Ingrid Robl ◽  
Miroslava Opekarovà ◽  
Widmar Tanner
Keyword(s):  
Helical Structure ◽  
Full Activity ◽  
C Terminus

scholarly journals Inhibition of Human Cytomegalovirus DNA Polymerase by C-Terminal Peptides from the UL54 Subunit

2003 ◽  
Vol 77 (15) ◽  
pp. 8336-8344 ◽  
Author(s):  
Arianna Loregian ◽  
Roberto Rigatti ◽  
Mary Murphy ◽  
Elisabetta Schievano ◽  
Giorgio Palu ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Helical Structure ◽  
Structural Similarity ◽  
Accessory Protein ◽  
Physical Interaction ◽  
Virus Growth ◽  
C Terminus ◽  
Simplex Virus ◽  
Carboxy Terminal

ABSTRACT In common with other herpesviruses, the human cytomegalovirus (HCMV) DNA polymerase contains a catalytic subunit (Pol or UL54) and an accessory protein (UL44) that is thought to increase the processivity of the enzyme. The observation that antisense inhibition of UL44 synthesis in HCMV-infected cells strongly inhibits viral DNA replication, together with the structural similarity predicted for the herpesvirus processivity subunits, highlights the importance of the accessory protein for virus growth and raises the possibility that the UL54/UL44 interaction might be a valid target for antiviral drugs. To investigate this possibility, overlapping peptides spanning residues 1161 to 1242 of UL54 were synthesized and tested for inhibition of the interaction between purified UL54 and UL44 proteins. A peptide, LPRRLHLEPAFLPYSVKAHECC, corresponding to residues 1221 to 1242 at the very C terminus of UL54, disrupted both the physical interaction between the two proteins and specifically inhibited the stimulation of UL54 by UL44. A mutant peptide lacking the two carboxy-terminal cysteines was markedly less inhibitory, suggesting a role for these residues in the UL54/UL44 interaction. Circular dichroism spectroscopy indicated that the UL54 C-terminal peptide can adopt a partially α-helical structure. Taken together, these results indicate that the two subunits of HCMV DNA polymerase most likely interact in a way which is analogous to that of the two subunits of herpes simplex virus DNA polymerase, even though there is no sequence homology in the binding site, and suggest that the UL54 peptide, or derivatives thereof, could form the basis for developing a new class of anti-HCMV inhibitors that act by disrupting the UL54/UL44 interaction.

Biological Properties of Synthetic Human Parathyroid Hormone: Effect of Deamidation at Position 76 on Agonist and Antagonist Activity*

Endocrinology ◽  
1991 ◽  
Vol 128 (5) ◽  
pp. 2583-2590 ◽  
Author(s):  
G. ZAMAN ◽  
P. W. SAPHIER ◽  
N. LOVERIDGE ◽  
T. KIMURA ◽  
S. SAKAKIBARA ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Biological Properties ◽  
Human Parathyroid Hormone ◽  
Antagonist Activity ◽  
Hormone Effect ◽  
Agonist And Antagonist

Diagnostic Limitations of Region-Specific Parathyroid Hormone Assays in the Investigation of Hypercalcaemia

1988 ◽  
Vol 25 (3) ◽  
pp. 275-279 ◽  
Author(s):  
J P Ashby ◽  
H Thakkar
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Sensitivity And Specificity ◽  
C Terminus ◽  
N Terminus ◽  
Degree Of Overlap ◽  
Sensitive Method

Assays for N-terminus, C-terminus and mid-molecule parathyroid hormone have been assessed with respect to their sensitivity and specificity in the diagnosis of primary hyperparathyroidism (1° HPT). The mid-molecule assay was the most sensitive method studied and only failed to identify one out of 30 patients with histologically proven 1° HPT. In all three assays there was some degree of overlap between results observed in 1° HPT and in patients with non-parathyroid hypercalcaemia, with results in the latter group sometimes falling well within the hyperparathyroid range. This study highlights the limitations of currently available methods and emphasises the need for caution in the interpretation of parathyroid hormone (PTH) measurements.

scholarly journals Activation of the Redox-regulated Chaperone Hsp33 by Domain Unfolding

2004 ◽  
Vol 279 (19) ◽  
pp. 20529-20538 ◽  
Author(s):  
Paul C. F. Graf ◽  
Maria Martinez-Yamout ◽  
Stephen VanHaerents ◽  
Hauke Lilie ◽  
H. Jane Dyson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Binding Site ◽  
Conformational Changes ◽  
Substrate Binding ◽  
Helical Structure ◽  
Activation Process ◽  
Spectroscopic Techniques ◽  
Substrate Binding Site ◽  
C Terminus ◽  
Dimerization Interface

The molecular chaperone Hsp33 inEscherichia coliresponds to oxidative stress conditions with the rapid activation of its chaperone function. On its activation pathway, Hsp33 progresses through three major conformations, starting as a reduced, zinc-bound inactive monomer, proceeding through an oxidized zinc-free monomer, and ending as a fully active oxidized dimer. While it is known that Hsp33 senses oxidative stress through its C-terminal four-cysteine zinc center, the nature of the conformational changes in Hsp33 that must take place to accommodate this activation process is largely unknown. To investigate these conformational rearrangements, we constructed constitutively monomeric Hsp33 variants as well as fragments consisting of the redox regulatory C-terminal domain of Hsp33. These proteins were studied by a combination of biochemical and NMR spectroscopic techniques. We found that in the reduced, monomeric conformation, zinc binding stabilizes the C terminus of Hsp33 in a highly compact, α-helical structure. This appears to conceal both the substrate-binding site as well as the dimerization interface. Zinc release without formation of the two native disulfide bonds causes the partial unfolding of the C terminus of Hsp33. This is sufficient to unmask the substrate-binding site, but not the dimerization interface, rendering reduced zinc-free Hsp33 partially active yet monomeric. Critical for the dimerization is disulfide bond formation, which causes the further unfolding of the C terminus of Hsp3 and allows the association of two oxidized Hsp33 monomers. This then leads to the formation of active Hsp33 dimers, which are capable of protecting cells against the severe consequences of oxidative heat stress.

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