title: Identification of Functional Regulatory Residues of the β -Lactam Inducible Penicillin Binding Protein in Methicillin-Resistant Staphylococcus aureus.
abstract: Resistance to methicillin by Staphylococcus aureus is a persistent clinical problem worldwide. A mechanism for resistance has been proposed in which methicillin resistant Staphylococcus aureus (MRSA) isolates acquired a new protein called β -lactam inducible penicillin binding protein (PBP-2'). The PBP-2' functions by substituting other penicillin binding proteins which have been inhibited by β -lactam antibiotics. Presently, there is no structural and regulatory information on PBP-2' protein. We conducted a complete structural and functional regulatory analysis of PBP-2' protein. Our analysis revealed that the PBP-2' is very stable with more hydrophilic amino acids expressing antigenic sites. PBP-2' has three striking regulatory points constituted by first penicillin binding site at Ser25, second penicillin binding site at Ser405, and finally a single metallic ligand binding site at Glu657 which binds to Zn(2+) ions. This report highlights structural features of PBP-2' that can serve as targets for developing new chemotherapeutic agents and conducting site direct mutagenesis experiments.
authors: Center for Bioinformatics & Computational Biology, Department of Biology, Jackson State University, Jackson, MS 39217, USA.
authors: Andreas N
authors: AN
authors: Mbah
authors: Raphael D
authors: RD
authors: Isokpehi
references: Antimicrob Agents Chemother. 2001 May;45(5):1323-36
references: 11302791
references: PLoS Pathog. 2011 Sep;7(9):e1002222
references: 21980283
references: Antimicrob Agents Chemother. 2000 Jun;44(6):1616-23
references: 10817718
references: Microb Drug Resist. 1997 Winter;3(4):409-13
references: 9442495
references: J Mol Biol. 1993 Dec 20;234(4):1158-70
references: 8263918
references: Antimicrob Agents Chemother. 1980 Sep;18(3):424-32
references: 6448580
references: J Proteomics. 2012 Jan 4;75(3):868-77
references: 22036931
references: Neuroreport. 2011 Nov 16;22(16):839-44
references: 21934536
references: Protein Eng. 1990 Dec;4(2):155-61
references: 2075190
references: Methods Enzymol. 1990;182:50-68
references: 2314256
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W469-73
references: 20513649
references: J Gen Microbiol. 1983 May;129(5):1247-60
references: 6352855
references: Nat Protoc. 2009;4(3):363-71
references: 19247286
references: Science. 1986 Oct 10;234(4773):179-86
references: 3018930
references: Genes Cells. 1997 Jan;2(1):13-28
references: 9112437
references: J Biol Chem. 2012 Oct 26;287(44):36854-63
references: 22977239
references: Proc Natl Acad Sci U S A. 1965 Oct;54(4):1133-41
references: 5219821
references: J Biol Chem. 1989 Oct 5;264(28):16700-12
references: 2506181
references: Proteins. 2006 Nov 1;65(2):305-16
references: 16927295
references: Antimicrob Agents Chemother. 1980 Nov;18(5):834-6
references: 6778388
references: J Bacteriol. 1989 Mar;171(3):1394-401
references: 2466033
references: Antimicrob Agents Chemother. 1982 Jul;22(1):172-5
references: 7125630
references: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10886-91
references: 11517340
references: Nature. 1966 Mar 5;209(5027):994-6
references: 5180132
references: Proteins. 2003 Sep 1;52(4):585-97
references: 12910458
references: Microb Drug Resist. 2001 Winter;7(4):349-61
references: 11822775
references: Antimicrob Agents Chemother. 1985 May;27(5):851-7
references: 3848294
references: PLoS One. 2011;6(7):e21614
references: 21789174
references: J Appl Toxicol. 2013 Aug;33(8):746-55
references: 22354777
references: Antimicrob Agents Chemother. 1994 Mar;38(3):447-54
references: 7911288
references: Antimicrob Agents Chemother. 1986 Jan;29(1):85-92
references: 3488015
references: Biol Pharm Bull. 1996 Mar;19(3):459-65
references: 8924919
references: FEBS Lett. 1987 Aug 31;221(1):167-71
references: 3305073
references: Antimicrob Agents Chemother. 1998 Mar;42(3):717-20
references: 9517962
references: J Bacteriol. 1999 May;181(9):2970-2
references: 10217796
references: J Bacteriol. 1991 Sep;173(18):5740-6
references: 1885547
references: Antimicrob Agents Chemother. 1981 May;19(5):726-35
references: 7294764
references: Antimicrob Agents Chemother. 2002 Apr;46(4):1147-52
references: 11897611
references: Adv Appl Bioinform Chem. 2013 May 10;6:15-27
references: 23696708
references: Antimicrob Agents Chemother. 2000 Jun;44(6):1549-55
references: 10817707
references: J Biochem. 1980 Dec;88(6):1895-8
references: 7462208
references: Antimicrob Agents Chemother. 1978 Apr;13(4):669-75
references: 352261
references: Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824-8
references: 6167991
references: Clin Infect Dis. 2001 May 15;32 Suppl 2:S114-32
references: 11320452
references: Antimicrob Agents Chemother. 1972 Nov;2(5):350-5
references: 4494489
references: Microbiol Mol Biol Rev. 1998 Mar;62(1):181-203
references: 9529891
references: J Mol Biol. 1982 May 5;157(1):105-32
references: 7108955
references: J Theor Biol. 2008 Sep 21;254(2):284-93
references: 18577389
references: J Am Chem Soc. 2011 Jul 20;133(28):10839-48
references: 21574608
references: Antimicrob Agents Chemother. 1996 Dec;40(12):2680-5
references: 9124822
references: J Am Chem Soc. 2004 Mar 24;126(11):3404-5
references: 15025450
references: Antimicrob Agents Chemother. 1999 Jun;43(6):1449-58
references: 10348769
references: Antimicrob Agents Chemother. 2003 Mar;47(3):1028-36
references: 12604538
references: Microbiol Mol Biol Rev. 1998 Mar;62(1):110-29
references: 9529889
references: Comput Biol Med. 2006 Feb;36(2):157-66
references: 16389075
references: Sci STKE. 2004 Sep 07;2004(250):RE13
references: 15367757
references: J Mol Biol. 2001 Apr 13;307(5):1419-26
references: 11292352
references: J Infect Dis. 1983 Mar;147(3):591
references: 6550616
references: J Bacteriol. 2001 Nov;183(22):6525-31
references: 11673420
references: FEBS Lett. 2012 Feb 17;586(4):455-8
references: 22289182
references: Clin Microbiol Rev. 1997 Oct;10(4):781-91
references: 9336672
references: J Bacteriol. 1965 Apr;89:1005-10
references: 14276086
references: Nat Rev Microbiol. 2009 Sep;7(9):629-41
references: 19680247
references: J Biol Chem. 2009 Sep 4;284(36):24406-14
references: 19535342
references: Sci Signal. 2012 Feb 14;5(211):ra14
references: 22337810
references: J Biochem. 2004 Jan;135(1):33-42
references: 14999007
references: J Med Microbiol. 1969 Aug;2(3):261-78
references: 5405709
references: J Phys Chem B. 2012 Jun 14;116(23):6670-82
references: 22352982
references: PLoS One. 2011;6(8):e23287
references: 21829724
references: Drug Target Insights. 2012;6:41-58
references: 23133313
references: Antimicrob Agents Chemother. 1992 Dec;36(12):2617-21
references: 1362343
references: J Antimicrob Chemother. 1999 Jan;43(1):15-22
references: 10381096
references: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7687-92
references: 12032344
references: J Bacteriol. 1985 Jan;161(1):243-8
references: 3881388
references: Proc Natl Acad Sci U S A. 1965 Jul;54(1):75-81
references: 5216369
references: Bioinformation. 2011;7(5):222-33
references: 22125390
references: Adv Exp Med Biol. 2012;946:87-112
references: 21948364
references: Antimicrob Agents Chemother. 1993 Jun;37(6):1219-26
references: 8328773
references: J Bacteriol. 1986 Feb;165(2):373-8
references: 3003024
references: Mol Microbiol. 1987 Jul;1(1):101-6
references: 3330753
references: Microbiol Mol Biol Rev. 1998 Dec;62(4):1079-93
references: 9841666
references: Eur J Clin Microbiol Infect Dis. 2001 Oct;20(10):685-97
references: 11757969
references: Anal Biochem. 1989 Nov 1;182(2):319-26
references: 2610349
references: Acta Crystallogr D Biol Crystallogr. 2004 May;60(Pt 5):849-59
references: 15103130
references: FEBS Lett. 1992 Feb 24;298(2-3):133-6
references: 1544435
references: J Bacteriol. 1989 Feb;171(2):874-9
references: 2536684
references: Antimicrob Agents Chemother. 2011 Jan;55(1):101-9
references: 20956585