In silico identification of novel bacterial ADP-ribosyltransferases

被引:22
作者
Masignani, V [1 ]
Balducci, E [1 ]
Serruto, D [1 ]
Veggi, D [1 ]
Aricò, B [1 ]
Comanducci, M [1 ]
Pizza, M [1 ]
Rappuoli, R [1 ]
机构
[1] IRIS, Chiron Vaccines, I-53100 Siena, Italy
关键词
ADP-ribosylating enzymes; genome analysis; secondary structure; Meningococcus; Listeria;
D O I
10.1078/1438-4221-00296
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
With the advent of the genomic era, identification of bacterial factors involved in virulence is a different challenge. Given the vast amount of information available on toxins, in terms of sequence and 3D structure, and thanks to the growing number of sequenced bacterial genomes, it is possible to proceed by homology criteria to predict novel toxins in different microorganisms. ADP-ribosyltransferases constitute a class of functionally conserved enzymes, which display toxic activity in a variety of bacterial pathogens. Since these proteins play a key role in pathogenesis, they have been extensively characterized and successfully used as vaccine components and mucosal adjuvants. Therefore, the application of in silico analyses to identify novel members of this class of enzymes represents an important challenge in the genomic era. To address this subject, different groups have recently pursued homology-based procedures to screen bacterial genomes for novel, yet undiscovered ADP-ribosylrransferases (ADPRTs) and have identified more than twenty novel ADPRTs in Gram-positive and Gram-negative bacteria. We have developed a novel pattern-based computational approach, which, flanked by secondary structure prediction tools, has allowed the identification of previously unrecognised putative ADPRTs. One of them, identified in Neisseria meningitidis has been extensively characterized and shown to possess the predicted enzymatic activity, suggesting a possible role of this protein in the virulence of Meningococcus.
引用
收藏
页码:471 / 478
页数:8
相关论文
共 28 条
[1]  
Althaus F R, 1987, Mol Biol Biochem Biophys, V37, P1
[2]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[3]  
ANTOINE R, 1994, J BIOL CHEM, V269, P6450
[4]   PHOTOAFFINITY-LABELING OF DIPHTHERIA-TOXIN FRAGMENT-A WITH NAD - STRUCTURE OF THE PHOTOPRODUCT AT POSITION-148 [J].
CARROLL, SF ;
MCCLOSKEY, JA ;
CRAIN, PF ;
OPPENHEIMER, NJ ;
MARSCHNER, TM ;
COLLIER, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (21) :7237-7241
[5]   AN NAD DERIVATIVE PRODUCED DURING TRANSFER-RNA SPLICING - ADP-RIBOSE 1''-2'' CYCLIC PHOSPHATE [J].
CULVER, GM ;
MCCRAITH, SM ;
ZILLMANN, M ;
KIERZEK, R ;
MICHAUD, N ;
LAREAU, RD ;
TURNER, DH ;
PHIZICKY, EM .
SCIENCE, 1993, 261 (5118) :206-208
[6]   Three conserved consensus sequences identify the NAD-binding site of ADP-ribosylating enzymes, expressed by eukaryotes, bacteria and T-even bacteriophages [J].
Domenighini, M ;
Rappuoli, R .
MOLECULAR MICROBIOLOGY, 1996, 21 (04) :667-674
[7]   COMMON FEATURES OF THE NAD-BINDING AND CATALYTIC SITE OF ADP-RIBOSYLATING TOXINS [J].
DOMENIGHINI, M ;
MAGAGNOLI, C ;
PIZZA, M ;
RAPPUOLI, R .
MOLECULAR MICROBIOLOGY, 1994, 14 (01) :41-50
[8]  
Glaser P, 2001, SCIENCE, V294, P849
[9]   CLONING, NUCLEOTIDE-SEQUENCE, AND EXPRESSION IN ESCHERICHIA-COLI OF THE EXOTOXIN-A STRUCTURAL GENE OF PSEUDOMONAS-AERUGINOSA [J].
GRAY, GL ;
SMITH, DH ;
BALDRIDGE, JS ;
HARKINS, RN ;
VASIL, ML ;
CHEN, EY ;
HEYNEKER, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (09) :2645-2649
[10]   Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex [J].
Han, S ;
Craig, JA ;
Putnam, CD ;
Carozzi, NB ;
Tainer, JA .
NATURE STRUCTURAL BIOLOGY, 1999, 6 (10) :932-936