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同: PBP

WordNet

executed with proper legal authority; "a binding contract"
the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
strip sewn over or along an edge for reinforcement or decoration
the capacity to attract and hold something
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
any of various antibiotics obtained from Penicillium molds (or produced synthetically) and used in the treatment of various infections and diseases

PrepTutorEJDIC

義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料
蛋白(たんばく)質
ペニシリン(坑生物質の一種)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/25 13:12:45」(JST)

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Ribbon representation of the atomic structure of Penicillin Binding Protein 3 from Pseudomonas aeruginosa (PDB 3OC2),^[1] image created with PyMol.

Penicillin core

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics (except for tabtoxinine-β-lactam, which inhibits glutamine synthetase) bind to PBPs, which are essential for bacterial cell wall biogenesis.

Diversity

There are a large number of PBPs, usually several in each organism, and they are found as both membrane-bound and cytoplasmic proteins. For example, Spratt (1977) reports that six different PBPs are routinely detected in all strains of E. coli ranging in molecular weight from 40,000 to 91,000.^[2] The different PBPs occur in different numbers per cell and have varied affinities for penicillin (see appendix). The PBPs are usually broadly classified into high-molecular-weight (HMW) and low-molecular-weight (LMW) categories.^[3] Proteins that have evolved from PBPs occur in many higher organisms and include the mammalian LACTB protein.^[4]

Function

PBPs are all involved in the final stages of the synthesis of peptidoglycan, which is the major component of bacterial cell walls. Bacterial cell wall synthesis is essential to growth, cell division (thus reproduction) and maintaining the cellular structure in bacteria. Inhibition of PBPs leads to irregularities in cell wall structure such as elongation, lesions, loss of selective permeability, and eventual cell death and lysis.

PBPs have been shown to catalyze a number of reactions involved in the process of synthesizing cross-linked peptidoglycan from lipid intermediates and mediating the removal of D-alanine from the precursor of peptidoglycan. Purified enzymes have been shown to catalyze the following reactions: D-alanine carboxypeptidase, peptidoglycan transpeptidase, and peptidoglycan endopeptidase. In all bacteria that have been studied, enzymes have been shown to catalyze more than one of the above reactions.^[2] The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (involved in formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (involved in cross-linking of the peptide subunits) and the serine at the active site is conserved in all members of the PBP family.^[3]

PBPs normally catalyze the cross-linking of the bacterial cell wall, but they can be permanently inhibited by penicillin and other β-lactam antibiotics. (NAM = N-acetylmuramic acid; NAG = N-acetylglucosamine)

Antibiotics

PBPs bind to β-lactam antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan.^[5] When they bind to penicillin, the β-lactam amide bond is ruptured to form a covalent bond with the catalytic serine residue at the PBPs active site. This is an irreversible reaction and inactivates the enzyme.

There has been a great deal of research into PBPs because of their role in antibiotics and resistance. Bacterial cell wall synthesis and the role of PBPs in its synthesis is a very good target for drugs of selective toxicity because the metabolic pathways and enzymes are unique to bacteria.^[6] Resistance to antibiotics has come about through overproduction of PBPs and formation of PBPs that have low affinity for penicillins (among other mechanisms such as lactamase production). Research on PBPs has led to the discovery of new semi-synthetic β-lactams, wherein altering the side-chains on the original penicillin molecule has increased the affinity of PBPs for penicillin, and, thus, increased effectiveness in bacteria with developing resistance.

Presence of the protein penicillin binding protein 2A (PBP2A) is responsible for the antibiotic resistance seen in methicillin-resistant Staphylococcus aureus (MRSA).

The β-lactam ring is a structure common to all β-lactam antibiotics.

References

^ Sainsbury, S., Bird, L., Rao, V., Shepherd, S.M., Stuart, D.I., Hunter, W.N., Owens, R.J., and Ren, J. (2011). "Crystal Structures of Penicillin-Binding Protein 3 from Pseudomonas aeruginosa: Comparison of Native and Antibiotic-Bound Forms". J.Mol.Biol. 405: 173–184. doi:10.1016/j.jmb.2010.10.024.
^ ^a ^b Spratt BG (1977). "Properties of the penicillin-binding proteins of Escherichia coli K12,.". Eur J Biochem 72 (2): 341–52. doi:10.1111/j.1432-1033.1977.tb11258.x. PMID 319999.
^ ^a ^b Basu J, Chattopadhyay R, Kundu M, Chakrabarti P (1992). "Purification and partial characterization of a penicillin-binding protein from Mycobacterium smegmatis.". J Bacteriol 174 (14): 4829–32. PMC 206282. PMID 1624470.
^ Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, Lindholm D, Thompson J, Eriksson O (2008). "Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy". MBC Evolutionary Biology 8: 16. doi:10.1186/1471-2148-8-26. PMC 2266909. PMID 18226203.
^ Nguyen-Distèche M, Leyh-Bouille M, Ghuysen JM (1982). "Isolation of the membrane-bound 26 000-Mr penicillin-binding protein of Streptomyces strain K15 in the form of a penicillin-sensitive D-alanyl-D-alanine-cleaving transpeptidase.". Biochem J 207 (1): 109–15. PMC 1153830. PMID 7181854.
^ Chambers HF (1999). "Penicillin-binding protein-mediated resistance in pneumococci and staphylococci.". J Infect Dis. 179 Suppl 2: S353–9. doi:10.1086/513854. PMID 10081507.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. β-ラクタム系抗生物質：作用機序、耐性および有害作用 beta lactam antibiotics mechanisms of action and resistance and adverse effects
2. メチシリン耐性黄色ブドウ球菌の微生物学 microbiology of methicillin resistant staphylococcus aureus
3. コアグラーゼ陰性ブドウ球菌による感染症の治療 treatment of infections due to coagulase negative staphylococci
4. 腸球菌における抗菌薬耐性の機構 mechanisms of antibiotic resistance in enterococci
5. 成人における侵襲性メチシリン耐性黄色ブドウ球菌感染症の治療 treatment of invasive methicillin resistant staphylococcus aureus infections in adults

English Journal

Proteomic Analysis of Cross Protection Provided between Cold and Osmotic Stress in Listeria monocytogenes.

Pittman JR1, Buntyn JO, Posadas G, Nanduri B, Pendarvis K, Donaldson JR.Author information 1Department of Biological Sciences and §Department of Basic Sciences, Mississippi State University , Mississippi State, Mississippi 39762, United States.AbstractListeria monocytogenes is a Gram-positive, foodborne pathogen responsible for approximately 28% of all food-related deaths each year in the United States. L. monocytogenes infections are linked to the consumption of minimally processed ready-to-eat (RTE) products such as cheese, deli meats, and cold-smoked finfish products. L. monocytogenes is resistant to stresses commonly encountered in the food-processing environment, including low pH, high salinity, oxygen content, and various temperatures. The purpose of this study was to determine if cells habituated at low temperatures would result in cross-protective effects against osmotic stress. We found that cells exposed to refrigerated temperatures prior to a mild salt stress treatment had increased survival in NaCl concentrations of 3%. Additionally, the longer the cells were pre-exposed to cold temperatures, the greater the increase in survival in 3% NaCl. A proteomics analysis was performed in triplicate in order to elucidate mechanisms involved in cold-stress induced cross protection against osmotic stress. Proteins involved in maintenance of the cell wall and cellular processes, such as penicillin binding proteins and osmolyte transporters, and processes involving amino acid metabolism, such as osmolyte synthesis, transport, and lipid biosynthesis, had the greatest increase in expression when cells were exposed to cold temperatures prior to salt. By gaining a better understanding of how this pathogen adapts physiologically to various environmental conditions, improvements can be made in detection and mitigation strategies.
Journal of proteome research.J Proteome Res.2014 Apr 4;13(4):1896-904. doi: 10.1021/pr401004a. Epub 2014 Mar 5.
Listeria monocytogenes is a Gram-positive, foodborne pathogen responsible for approximately 28% of all food-related deaths each year in the United States. L. monocytogenes infections are linked to the consumption of minimally processed ready-to-eat (RTE) products such as cheese, deli meats, and cold
PMID 24564473

Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins.

Kumar KM1, Anbarasu A, Ramaiah S.Author information 1School of Biosciences and Technology, VIT University, Vellore - 632014, Tamil Nadu, India. sudhaanand@vit.ac.in.AbstractBacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expressing drug insensitive PBPs rendering β-lactam antibiotics ineffective and (ii) production of β-lactamases along with alteration of their specificities. Thus, there is an urgent need to develop newer β-lactams to overcome the challenge of bacterial resistance. Therefore the present study aims to identify the binding affinity of β-lactam antibiotics with different types of PBPs and β-lactamases. In this study, cephalosporins and carbapenems are docked into PBP2a of Staphylococcus aureus, PBP2b and PBP2x of Streptococcus pneumoniae and SHV-1 β-lactamase of Escherichia coli. The results reveal that Ceftobiprole can efficiently bind to PBP2a, PBP2b and PBP2x and not strongly to SHV-1 β-lactamase. Furthermore, molecular dynamics (MD) simulations are performed to refine the binding mode of the docked complex structure and to observe the differences in the stability of free PBP2x and Ceftobiprole bound PBP2x. MD simulation supports the greater stability of the Ceftobiprole-PBP2x complex compared to free PBP2x. This work demonstrates that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β-lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.
Molecular bioSystems.Mol Biosyst.2014 Apr 4;10(4):891-900. doi: 10.1039/c3mb70537d. Epub 2014 Feb 6.
Bacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pat
PMID 24503740

Can Molecular Dynamics and QM/MM solve the Penicillin Binding Protein Protonation Puzzle?

Hargis JC, White JK, Chen Y, Woodcock HL.AbstractBenzylpenicillin, a member of the β-lactam antibiotic class, has been widely used to combat bacterial infections since 1947. The general mechanism is well known: a serine protease enzyme (i.e. DD-peptidase) forms a long lasting intermediate with the lactam ring of the antibiotic known as acylation, effectively preventing biosynthesis of the bacterial cell wall. Despite this overall mechanistic understanding, many details of binding and catalysis are unclear. Specifically, there is ongoing debate about active site protonation states and the role of general acids / bases in the reaction. Herein, a unique combination of MD simulations, QM/MM minimizations, and QM/MM orbital analyses is combined with systematic variation of active site residue protonation states. Critical interactions that maximize the stability of the bound inhibitor are examined and used as metrics. This approach was validated by examining cefoxitin interactions in the CTX-M β-lactamase from E.coli and compared to an ultra high-resolution (0.88 Å) crystal structure. Upon confirming the approach used, an investigation of the pre-acylated Streptomyces R61 active site with bound benzylpenicillin was performed; varying the protonation states of His298 and Lys65. We concluded that protonated His298 and deprotonated Lys65 are most likely to exist in the R61 active site.
Journal of chemical information and modeling.J Chem Inf Model.2014 Apr 3. [Epub ahead of print]
Benzylpenicillin, a member of the β-lactam antibiotic class, has been widely used to combat bacterial infections since 1947. The general mechanism is well known: a serine protease enzyme (i.e. DD-peptidase) forms a long lasting intermediate with the lactam ring of the antibiotic known as acylation,
PMID 24697903

Japanese Journal

New Approaches to Drug Discovery for Combating MRSA

Chemical and Pharmaceutical Bulletin 64(2), 104-111, 2016
NAID 130005121716

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 19(1), 50-56, 2013-02-01
NAID 10031155818

侵襲性肺炎球菌感染症の小児から分離された Streptococcus pneumoniae の抗菌薬感受性

感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases 87(1), 1-5, 2013-01-20
NAID 10031176211

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リンク元	「ペニシリン結合タンパク」
拡張検索	「penicillin-binding proteins」
関連記事	「binding」「binding protein」

「ペニシリン結合タンパク」

Penicillin-binding protein, dimerisation domain
Identifiers
Symbol	PBP_dimer
Pfam	PF03717
InterPro	IPR005311
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Penicillin-binding protein, transpeptidase
Identifiers
Symbol	PCN-bd_Tpept
Pfam	PF00905
InterPro	IPR001460
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary