3 Biotech. 2015 Jun;5(3):317-336. doi: 10.1007/s13205-014-0231-z. Epub 2014 Jun 17.
Structure-based functional annotation of putative conserved proteins having lyase activity from Haemophilus influenzae.
3 Biotech
Mohd Shahbaaz, Faizan Ahmad, Md Imtaiyaz Hassan
Affiliations
Affiliations
- Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India.
- Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
- Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. [email protected].
PMID: 28324295
PMCID: PMC4434415 DOI: 10.1007/s13205-014-0231-z
Abstract
Haemophilus influenzae is a small pleomorphic Gram-negative bacteria which causes several chronic diseases, including bacteremia, meningitis, cellulitis, epiglottitis, septic arthritis, pneumonia, and empyema. Here we extensively analyzed the sequenced genome of H. influenzae strain Rd KW20 using protein family databases, protein structure prediction, pathways and genome context methods to assign a precise function to proteins whose functions are unknown. These proteins are termed as hypothetical proteins (HPs), for which no experimental information is available. Function prediction of these proteins would surely be supportive to precisely understand the biochemical pathways and mechanism of pathogenesis of Haemophilus influenzae. During the extensive analysis of H. influenzae genome, we found the presence of eight HPs showing lyase activity. Subsequently, we modeled and analyzed three-dimensional structure of all these HPs to determine their functions more precisely. We found these HPs possess cystathionine-β-synthase, cyclase, carboxymuconolactone decarboxylase, pseudouridine synthase A and C, D-tagatose-1,6-bisphosphate aldolase and aminodeoxychorismate lyase-like features, indicating their corresponding functions in the H. influenzae. Lyases are actively involved in the regulation of biosynthesis of various hormones, metabolic pathways, signal transduction, and DNA repair. Lyases are also considered as a key player for various biological processes. These enzymes are critically essential for the survival and pathogenesis of H. influenzae and, therefore, these enzymes may be considered as a potential target for structure-based rational drug design. Our structure-function relationship analysis will be useful to search and design potential lead molecules based on the structure of these lyases, for drug design and discovery.
Keywords: Function prediction; Gene annotation; Haemophilus influenzae; Hypothetical protein; Sequence analysis; Structure analysis; Structure–function relationship
References
- Proteins. 2006 Aug 15;64(3):643-51 - PubMed
- Genomics Proteomics Bioinformatics. 2006 Feb;4(1):42-7 - PubMed
- Mol Cell. 2006 Nov 17;24(4):535-45 - PubMed
- Genome Res. 2002 Oct;12(10):1619-23 - PubMed
- Gene. 2014 Jun 10;543(1):93-100 - PubMed
- Nucleic Acids Res. 2012 Jan;40(Database issue):D290-301 - PubMed
- J Mol Biol. 2001 Jan 19;305(3):567-80 - PubMed
- Nature. 2003 Dec 18;426(6968):884-90 - PubMed
- Comp Funct Genomics. 2001;2(1):14-8 - PubMed
- Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W116-20 - PubMed
- RNA. 2002 Oct;8(10):1253-66 - PubMed
- Nucleic Acids Res. 2013 Jan;41(Database issue):D490-8 - PubMed
- BMC Microbiol. 2005 Oct 07;5:58 - PubMed
- Trends Biochem Sci. 1997 Nov;22(11):442-4 - PubMed
- Cold Spring Harb Symp Quant Biol. 2001;66:147-59 - PubMed
- DNA Cell Biol. 2002 Apr;21(4):281-95 - PubMed
- J Nat Sci Biol Med. 2013 Jan;4(1):51-6 - PubMed
- J Comput Chem. 2009 Jul 30;30(10):1545-614 - PubMed
- Clin Microbiol Rev. 2001 Apr;14(2):336-63 - PubMed
- Mol Cell. 2003 Sep;12(3):689-98 - PubMed
- Future Microbiol. 2010 Mar;5(3):455-69 - PubMed
- Curr Opin Pulm Med. 2006 Mar;12(2):118-24 - PubMed
- J Biochem. 2000 Jul;128(1):29-38 - PubMed
- Nat Protoc. 2007;2(4):953-71 - PubMed
- Nucleic Acids Res. 2003 Jul 1;31(13):3692-7 - PubMed
- Trends Plant Sci. 2001 Feb;6(2):78-84 - PubMed
- Bioinformatics. 2005 May 1;21(9):1908-16 - PubMed
- Pac Symp Biocomput. 2003;:228-39 - PubMed
- Bioinformatics. 2007 Sep 15;23(18):2353-60 - PubMed
- J Biol Chem. 1999 Aug 6;274(32):22225-30 - PubMed
- Proteins. 2009 Nov 15;77(3):499-508 - PubMed
- Bioinformatics. 2005 May 15;21(10):2522-4 - PubMed
- Int J Mol Sci. 2012;13(6):7109-37 - PubMed
- RNA. 2003 Jun;9(6):711-21 - PubMed
- FEMS Microbiol Lett. 2005 Dec 15;253(2):193-9 - PubMed
- Environ Microbiol. 2004 Jun;6(6):552-67 - PubMed
- Adv Second Messenger Phosphoprotein Res. 1993;27:109-62 - PubMed
- Bioinformatics. 2010 Jul 1;26(13):1608-15 - PubMed
- Chem Biol Drug Des. 2007 Sep;70(3):261-7 - PubMed
- Curr Opin Biotechnol. 2000 Feb;11(1):31-5 - PubMed
- Nat Rev Drug Discov. 2002 Jul;1(7):493-502 - PubMed
- EMBO J. 1986 Apr;5(4):823-6 - PubMed
- Nucleic Acids Res. 2012 Jul;40(Web Server issue):W471-7 - PubMed
- Nucleic Acids Res. 1996 Jun 15;24(12):2411-5 - PubMed
- Clin Chest Med. 2005 Mar;26(1):47-55 - PubMed
- J Mol Med (Berl). 2000;78(5):269-81 - PubMed
- Rev Infect Dis. 1984 Mar-Apr;6 Suppl 1:S21-4 - PubMed
- RNA. 2004 Jul;10(7):1026-33 - PubMed
- Am Rev Respir Dis. 1992 Oct;146(4):1067-83 - PubMed
- Nucleic Acids Res. 2012 Jan;40(Database issue):D302-5 - PubMed
- J Biol Chem. 2002 Jun 14;277(24):22018-24 - PubMed
- Science. 1995 Jul 28;269(5223):496-512 - PubMed
- J Biol Chem. 1989 May 25;264(15):8597-601 - PubMed
- J Biol Chem. 1995 Jan 6;270(1):1-4 - PubMed
- Nucleic Acids Res. 2009 Jul;37(Web Server issue):W202-8 - PubMed
- Curr Opin Microbiol. 2004 Apr;7(2):185-91 - PubMed
- Nat Protoc. 2010 Apr;5(4):725-38 - PubMed
- J Pept Sci. 2007 Dec;13(12):849-55 - PubMed
- Infect Disord Drug Targets. 2007 Mar;7(1):19-27 - PubMed
- Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W89-93 - PubMed
- RNA. 2004 Feb;10(2):231-9 - PubMed
- Cell Mol Life Sci. 2004 Jun;61(12):1401-26 - PubMed
- Cell. 2001 Dec 28;107(7):929-39 - PubMed
- Annu Rev Biophys Biomol Struct. 2000;29:291-325 - PubMed
- Nucleic Acids Res. 2012 Jan;40(Database issue):D370-6 - PubMed
- Arch Biochem Biophys. 1978 Jan 30;185(2):584-91 - PubMed
- Bioinformatics. 2013 Oct 15;29(20):2588-95 - PubMed
- J Mol Biol. 1990 Oct 5;215(3):403-10 - PubMed
- Trends Biochem Sci. 1997 Jan;22(1):12-3 - PubMed
- Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5361-6 - PubMed
- J Mol Biol. 2001 Nov 2;313(4):903-19 - PubMed
- Acta Crystallogr D Biol Crystallogr. 2001 Sep;57(Pt 9):1209-18 - PubMed
- Nucleic Acids Res. 2012 Jan;40(Database issue):D306-12 - PubMed
- Nat Struct Biol. 2002 May;9(5):353-8 - PubMed
- Am J Physiol Cell Physiol. 2005 Dec;289(6):C1369-78 - PubMed
- Nucleic Acids Res. 2007 Jul;35(Web Server issue):W573-7 - PubMed
- Bioinformatics. 2010 Jan 1;26(1):46-52 - PubMed
- Int J Comput Biol Drug Des. 2011;4(4):373-86 - PubMed
- Proteins. 2011;79 Suppl 10:161-71 - PubMed
- J Mol Biol. 1963 Jul;7:95-9 - PubMed
- Nucleic Acids Res. 2005 Jan 1;33(Database issue):D226-9 - PubMed
- Proteins. 2009 Dec;77(4):778-95 - PubMed
- J Biol Chem. 1991 Jul 15;266(20):12971-5 - PubMed
- FEBS Lett. 2000 Aug 25;480(1):42-8 - PubMed
- Biochemistry. 2004 Apr 20;43(15):4454-63 - PubMed
- Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9 - PubMed
- Curr Opin Struct Biol. 2003 Feb;13(1):49-55 - PubMed
- Comput Appl Biosci. 1997 Aug;13(4):425-30 - PubMed
- RNA. 1999 Jun;5(6):751-63 - PubMed
- RNA. 2003 May;9(5):574-85 - PubMed
- Microbiology. 2004 Dec;150(Pt 12):3923-33 - PubMed
- Nucleic Acids Res. 1999 Jan 1;27(1):254-6 - PubMed
- J Biomol NMR. 1996 Dec;8(4):477-86 - PubMed
- J Mol Biol. 1989 Jul 5;208(1):1-22 - PubMed
- Nat Struct Biol. 2000 Jan;7(1):23-7 - PubMed
- Proc Natl Acad Sci U S A. 1990 Dec;87(23):9391-5 - PubMed
- Nucleic Acids Res. 2004 Oct 12;32(18):5452-63 - PubMed
- Nucleic Acids Res. 2005 Jan 1;33(Database issue):D284-8 - PubMed
- Science. 1972 Aug 4;177(4047):401-8 - PubMed
- Proteins. 2011;79 Suppl 10:6-20 - PubMed
- Bioinformatics. 2001 Sep;17(9):849-50 - PubMed
- BMC Struct Biol. 2009 May 28;9:37 - PubMed
- Proc Natl Acad Sci U S A. 1980 Jul;77(7):3879-83 - PubMed
- Microb Pathog. 2004 Jan;36(1):25-33 - PubMed
- J Bacteriol. 1998 Mar;180(5):1072-81 - PubMed
- Bioinformatics. 2011 Aug 1;27(15):2076-82 - PubMed
- J Leukoc Biol. 2007 Feb;81(2):393-400 - PubMed
- Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W244-8 - PubMed
- PLoS One. 2013 Dec 31;8(12):e84263 - PubMed
- BMC Bioinformatics. 2008 Jan 28;9:62 - PubMed
- Nucleic Acids Res. 2012 Jan;40(Database issue):D313-20 - PubMed
- Methods Mol Biol. 2012;815:25-38 - PubMed
- Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 - PubMed
- Structure. 2008 Dec 10;16(12):1755-63 - PubMed
- Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W526-31 - PubMed
- Infect Immun. 2004 Jun;72(6):3310-4 - PubMed
- Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8 - PubMed
- Methods Mol Biol. 2008;413:91-121 - PubMed
- Curr Protoc Protein Sci. 2007 Nov;Chapter 2:Unit 2.9 - PubMed
- Protein Sci. 2000 Dec;9(12):2344-53 - PubMed
Publication Types