Disease relevance of PBP

• The recent structural determination of Escherichia coli penicillin-binding protein 5 (PBP 5) provides the opportunity for detailed structure-function studies of this enzyme [1].

High impact information on PBP

• PEBP is a soluble cytoplasmic protein, also associated with plasma and reticulum membranes of numerous cell types [2].
• The hippocampal cholinergic neurostimulating peptide, the N-terminal fragment of the secreted phosphatidylethanolamine-binding protein, possesses a new biological activity on cardiac physiology [2].
• In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model [2].
• The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system [2].
• Previously, we purified a beta-pol promoter ATF/CRE-binding protein (named palindrome-binding protein or PBP) from bovine testes and found that this protein is a beta-pol promoter transcriptional activator in vitro using a HeLa nuclear extract transcription system (Widen, S. G., and Wilson, S. H. (1991) Biochemistry 30, 6296-6305) [3].

Biological context of PBP

• The expression of PEBP and related proteins seems to be correlated with development and cell morphogenesis, however [4].
• In this study, we determined the mechanism of in vitro transcriptional activation by this purified PBP [3].
• A possible role for PBP in membrane biogenesis and maintenance of antigen segregation in spermatozoa is discussed [5].
• PBP 5 demonstrated linear reaction kinetics for up to several hours [1].
• Based on its structure, similarity to Class A beta-lactamases, and results from mutagenesis studies, the acidic and basic limbs of the pH profile of PBP 5 are assigned to Lys-47 and Lys-213, respectively [1].

Anatomical context of PBP

• Spermatozoa, on the other hand, contained significant amounts of PBP that could be solubilized by washing cells in dissociating reagents or high-salt solutions [5].
• However, when PBP cDNAs from testis and epididymis were cloned and sequenced, they did not contain a signal peptide and only one size of transcript was obtained on Northern blots of RNAs from liver, brain, placenta, testis and epididymis [5].
• PBP is ubiquitous in tissue cytosols but is not present in blood serum, lymph or milk [5].
• These results indicate that, contrary to previous interpretations, PBP is not secreted by classical pathways in either the testis or epididymis but that its presence in CEP and rete testis fluid is attributable largely to release from spermatozoa [5].
• PBP 5 did not demonstrate a significant preference against a simple set of five alpha- and epsilon-substituted L-Lys-D-Ala-D-Ala derivatives, suggesting that PBP 5 lacks specificity for the cross-linked state of cell wall substrates [1].

Associations of PBP with chemical compounds

• PEBP binds to phosphatidylethanolamine and nucleotides in vitro, but its biological function in vivo is not yet known [4].
• Nevertheless, in PEBP, a small cavity close to the protein surface has a high affinity for anions, such as phosphate and acetate, and also phosphorylethanolamine [4].
• The strong conservation of a binding pocket at one end of this sheet which is capable of binding phosphoryl ligands, suggests the biological effects of CEN, like PEBP, arise from the ability of this region to form complexes with phosphorylated ligands, hence interfering with kinases and their effectors [6].
• The unique binding mode of IC toward the cognate proteinase provides insights into the inhibitory mechanism of PEBPs toward serine proteinases and into the specific biological functions of IC belonging to the PEBP family as well [7].
• The equilibrium behaviour of the bovine phosphatidylethanolamine-binding protein (PEBP) has been studied under various conditions of pH, temperature and urea concentration [8].

Other interactions of PBP

• To obtain new insights into the PEBP family and its potential functions, we initiated a crystallographic study of bovine brain PEPB [4].

References