The Structure of the First Representative of Pfam Family PF06475 Reveals a New Fold with Possible Involvement in Glycolipid Metabolism

The crystal structure of PA1994 from Pseudomonas aeruginosa, a member of the Pfam PF06475 family classified as a domain of unknown function (DUF1089), reveals a novel fold comprising a 15-stranded β-sheet wrapped around a single α-helix that assembles into a tight dimeric arrangement. The remote structural similarity to lipoprotein localization factors, in addition to the presence of an acidic pocket that is conserved in DUF1089 homologs, phospholipid-binding and sugar-binding proteins, indicate a role for PA1994 and the DUF1089 family in glycolipid metabolism. Genome-context analysis lends further support to the involvement of this family of proteins in glycolipid metabolism and indicates possible activation of DUF1089 homologs under conditions of bacterial cell-wall stress or host-pathogen interactions.

Citing Articles

Proteomics and bioinformatics analysis reveal potential roles of cadmium-binding proteins in cadmium tolerance and accumulation of .

Chuanboon K, Nakorn P, Pannengpetch S, Laengsri V, Nuchnoi P, Isarankura-Na-Ayudhya C PeerJ. 2019; 7:e6904.

PMID: 31534833 PMC: 6727835. DOI: 10.7717/peerj.6904.

Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence.

Herrou J, Willett J, Fiebig A, Czyz D, Cheng J, Ultee E J Bacteriol. 2019; 201(12).

PMID: 30936371 PMC: 6531618. DOI: 10.1128/JB.00134-19.

Pharmacoproteomics Profile in Response to Acamprosate Treatment of an Alcoholism Animal Model.

Germany C, Reker A, Hinton D, Oliveros A, Shen X, Andres-Beck L Proteomics. 2018; 18(7):e1700417.

PMID: 29437267 PMC: 6287941. DOI: 10.1002/pmic.201700417.

Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects.

Chartier M, Morency L, Zylber M, Najmanovich R BMC Pharmacol Toxicol. 2017; 18(1):18.

PMID: 28449705 PMC: 5408384. DOI: 10.1186/s40360-017-0128-7.

IsoCleft Finder - a web-based tool for the detection and analysis of protein binding-site geometric and chemical similarities.

Kurbatova N, Chartier M, Zylber M, Najmanovich R F1000Res. 2014; 2:117.

PMID: 24555058 PMC: 3892921. DOI: 10.12688/f1000research.2-117.v2.

References

Antikainen J, Kuparinen V, Kupannen V, Lahteenmaki K, Korhonen T . pH-dependent association of enolase and glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus crispatus with the cell wall and lipoteichoic acids. J Bacteriol. 2007; 189(12):4539-43. PMC: 1913374. DOI: 10.1128/JB.00378-07. View

Thoden J, Timson D, Reece R, Holden H . Molecular structure of human galactose mutarotase. J Biol Chem. 2004; 279(22):23431-7. DOI: 10.1074/jbc.M402347200. View

Bricogne G, Vonrhein C, Flensburg C, Schiltz M, Paciorek W . Generation, representation and flow of phase information in structure determination: recent developments in and around SHARP 2.0. Acta Crystallogr D Biol Crystallogr. 2003; 59(Pt 11):2023-30. DOI: 10.1107/s0907444903017694. View

LeMagueres P, Im H, Dvorak A, Strych U, Benedik M, Krause K . Crystal structure at 1.45 A resolution of alanine racemase from a pathogenic bacterium, Pseudomonas aeruginosa, contains both internal and external aldimine forms. Biochemistry. 2003; 42(50):14752-61. DOI: 10.1021/bi030165v. View

Schaumburg J, Diekmann O, Hagendorff P, Bergmann S, Rohde M, Hammerschmidt S . The cell wall subproteome of Listeria monocytogenes. Proteomics. 2004; 4(10):2991-3006. DOI: 10.1002/pmic.200400928. View

Muthaiyan A, Silverman J, Jayaswal R, Wilkinson B . Transcriptional profiling reveals that daptomycin induces the Staphylococcus aureus cell wall stress stimulon and genes responsive to membrane depolarization. Antimicrob Agents Chemother. 2007; 52(3):980-90. PMC: 2258546. DOI: 10.1128/AAC.01121-07. View

Oguchi Y, Takeda K, Watanabe S, Yokota N, Miki K, Tokuda H . Opening and closing of the hydrophobic cavity of LolA coupled to lipoprotein binding and release. J Biol Chem. 2008; 283(37):25414-25420. DOI: 10.1074/jbc.M804736200. View

Grochulski P, Li Y, Schrag J, Cygler M . Two conformational states of Candida rugosa lipase. Protein Sci. 1994; 3(1):82-91. PMC: 2142478. DOI: 10.1002/pro.5560030111. View

Smoot D . How does Helicobacter pylori cause mucosal damage? Direct mechanisms. Gastroenterology. 1997; 113(6 Suppl):S31-4; discussion S50. DOI: 10.1016/s0016-5085(97)80008-x. View

10.

Sri Krishna S, Weekes D, Bakolitsa C, Elsliger M, Wilson I, Godzik A . TOPSAN: use of a collaborative environment for annotating, analyzing and disseminating data on JCSG and PSI structures. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010; 66(Pt 10):1143-7. PMC: 2954197. DOI: 10.1107/S1744309110035736. View

11.

Sheldrick G . A short history of SHELX. Acta Crystallogr A. 2007; 64(Pt 1):112-22. DOI: 10.1107/S0108767307043930. View

12.

Krissinel E, Henrick K . Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2256-68. DOI: 10.1107/S0907444904026460. View

13.

Painter J, Merritt E . Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr D Biol Crystallogr. 2006; 62(Pt 4):439-50. DOI: 10.1107/S0907444906005270. View

14.

Diamant S, Eliahu N, Rosenthal D, Goloubinoff P . Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses. J Biol Chem. 2001; 276(43):39586-91. DOI: 10.1074/jbc.M103081200. View

15.

Cohen A, Ellis P, Miller M, Deacon A, Phizackerley R . An automated system to mount cryo-cooled protein crystals on a synchrotron beam line, using compact sample cassettes and a small-scale robot. J Appl Crystallogr. 2014; 35(6):720-726. PMC: 4041710. DOI: 10.1107/s0021889802016709. View

16.

Marland Z, Beddoe T, Zaker-Tabrizi L, Lucet I, Brammananth R, Whisstock J . Hijacking of a substrate-binding protein scaffold for use in mycobacterial cell wall biosynthesis. J Mol Biol. 2006; 359(4):983-97. DOI: 10.1016/j.jmb.2006.04.012. View

17.

Yancey P . Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol. 2005; 208(Pt 15):2819-30. DOI: 10.1242/jeb.01730. View

18.

Davis I, Murray L, Richardson J, Richardson D . MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 2004; 32(Web Server issue):W615-9. PMC: 441536. DOI: 10.1093/nar/gkh398. View

19.

Grochulski P, Bouthillier F, Kazlauskas R, Serreqi A, Schrag J, Ziomek E . Analogs of reaction intermediates identify a unique substrate binding site in Candida rugosa lipase. Biochemistry. 1994; 33(12):3494-500. DOI: 10.1021/bi00178a005. View

20.

Bengoechea J, Zhang L, Toivanen P, Skurnik M . Regulatory network of lipopolysaccharide O-antigen biosynthesis in Yersinia enterocolitica includes cell envelope-dependent signals. Mol Microbiol. 2002; 44(4):1045-62. DOI: 10.1046/j.1365-2958.2002.02940.x. View