Mutation in angiotensin II type 1 receptor disrupts its binding to angiotensin II leading to hypotension: An insight into hydrogen bonding patterns

doi:10.1007/s11515-012-1241-z

Front Biol

2012, Vol. 7

Issue (5) : 477-484 https://doi.org/10.1007/s11515-012-1241-z

RESEARCH ARTICLE

Mutation in angiotensin II type 1 receptor disrupts its binding to angiotensin II leading to hypotension: An insight into hydrogen bonding patterns

Arpita KUNDU, Sudha RAMAIAH, Anand ANBARASU(

)

Medical & Biological Computing Laboratory, School of Biosciences and Technology, VIT University, Vellore–632014, Tamil Nadu, India

Download: PDF(290 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

To understand the role of angiotensin II type 1 receptor gene (AGTR1) gene products in relation to hypotension we have analyzed the single nucleotide polymorphisms (SNPs) associated with this gene. This can help us to understand the genetic variations that can alter the function of the gene products. In this present study, we report the polymorphic variant associated with AGTR1 and its weak interaction with angiotensin II (AngII) which leads to hypotension. Out of 1318 SNPs, six are found to be non-synonymous, of which rs1064533 shows significant damaging effect. A missense mutation (T1255G), i.e., from thymine to guanine for rs1064533 in AGTR1 gene results in amino acid substitution from cysteine (Cys) to tryptophan (Trp) in the receptor protein. A strong hydrogen bond exists between Cys289 of native AGTR1 protein and glutamine 167 of AngII. Interestingly, it is replaced by a weak hydrogen bond in the mutant protein between Trp289 (mutant residue) and serine 340. Such a substitution from small, hydrophilic to bulky, hydrophobic residue in AGTR1 protein results in reduced binding affinity of the receptor protein with AngII, leading to hypotension. The results presented from this in silico study will open up new prospect for genetic analysis of AGTR1 gene and will be beneficial to the researchers for understanding the role played by AGTR1 gene in hypotension disease.

Keywords AGTR1 AngII hypotension rs1064533 cysteine tryptophan

Corresponding Author(s): ANBARASU Anand,Email:aanand@vit.ac.in

Issue Date: 01 October 2012

Cite this article:

Sudha RAMAIAH,Anand ANBARASU,Arpita KUNDU. Mutation in angiotensin II type 1 receptor disrupts its binding to angiotensin II leading to hypotension: An insight into hydrogen bonding patterns[J]. Front Biol, 2012, 7(5): 477-484.

URL:

https://academic.hep.com.cn/fib/EN/10.1007/s11515-012-1241-z
https://academic.hep.com.cn/fib/EN/Y2012/V7/I5/477

Tab.1 nsSNPs with their corresponding amino acid changes and FS scores

Tab.2 Functional prediction of nsSNPs by F-SNP database

Fig.1 The native protein structure of AGTR1with Cys (289) and mutant protein structure of AGTR1 with Trp (289) for SNP rs1064533.

Fig.2 Protein–protein interactions of AGTR1 and AngII. (A) Hydrogen bond with distance of 2.46? between sulfhydryl group at gamma position (SG) of Cys289 in native AGTR1 and oxygen (O) of Gln167 in AngII. Another hydrogen bond with distance of 2.42? between SG of Cys289 in native AGTR1 and nitrogen (N) of Gln167 in AngII. (B) Hydrogen bond with distance of 3.31? between nitrogen at epsilon1 position (NE1) of Trp289 in mutant AGTR1 and hydroxyl group at gamma position (OG) of Ser340 in AngII

1	Anbarasu A, Anand S, Mathew L, Rao S (2006). Computation of non-covalent interactions in TNF proteins and interleukins. Cytokine , 35(5-6): 263–269 doi: 10.1016/j.cyto.2006.09.005 pmid:17055289
2	Anbarasu A, Anand S, Mathew L, Sethumadhavan R (2007). Influence of cation-π interactions on RNA-binding proteins. Int J Biol Macromol , 40(5): 479–483 doi: 10.1016/j.ijbiomac.2006.11.008 pmid:17197018
3	Anbarasu A, Sethumadhavan R (2007). Exploring the role of cation-π interactions in glycoproteins lipid-binding proteins and RNA-binding proteins. J Theor Biol , 247(2): 346–353 doi: 10.1016/j.jtbi.2007.02.018 pmid:17451749
4	Ausiello G, Cesareni G, Helmer-Citterich M (1997). ESCHER: a new docking procedure applied to the reconstruction of protein tertiary structure. Proteins , 28(4): 556–567 doi: 10.1002/(SICI)1097-0134(199708)28:4<556::AID-PROT9>3.0.CO;2-7 pmid:9261871
5	Benner S A, Cannarozzi G, Gerloff D, Turcotte M, Chelvanayagam G (1997). Bona fide predictions of protein secondary structure using transparent analyses of multiple sequence alignments. Chem Rev , 97(8): 2725–2844 doi: 10.1021/cr940469a pmid:11851479
6	Berry C, Touyz R, Dominiczak A F, Webb R C, Johns D G (2001). Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol Heart Circ Physiol , 281(6): H2337–H2365 pmid:11709400
7	Cartegni L, Wang J, Zhu Z, Zhang M Q, Krainer A R (2003). ESEfinder: A web resource to identify exonic splicing enhancers. Nucleic Acids Res , 31(13): 3568–3571 doi: 10.1093/nar/gkg616 pmid:12824367
8	Eswar N, Webb B, Marti-Renom M A, Madhusudhan M S, Eramian D, Shen M Y, Pieper U, Sali A (2007). Comparative protein structure modeling using MODELLER. Curr Protoc Protein Sci , Chapter 2(9): 2, 9 pmid:18429317
9	Fairbrother W G, Yeh R F, Sharp P A, Burge C B (2002). Predictive identification of exonic splicing enhancers in human genes. Science , 297(5583): 1007–1013 doi: 10.1126/science.1073774 pmid:12114529
10	Fairbrother W G, Yeo G W, Yeh R, Goldstein P, Mawson M, Sharp P A, Burge C B (2004). RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons. Nucleic Acids Res , 32(Web ServerWeb Server issue): W187-90 doi: 10.1093/nar/gkh393 pmid:15215377
11	Fernandez-Recio J, Totrov M, Abagyan R (2002). Soft protein-protein docking in internal coordinates. Protein Sci , 11(2): 280–291 doi: 10.1110/ps.19202 pmid:11790838
12	Fiser A, Sali A (2003). Modeller: generation and refinement of homology-based protein structure models. Methods Enzymol , 374: 461–491 doi: 10.1016/S0076-6879(03)74020-8 pmid:14696385
13	Gallivan J P, Dougherty D A (1999). Cation-π interactions in structural biology. Proc Natl Acad Sci USA , 96(17): 9459–9464 doi: 10.1073/pnas.96.17.9459 pmid:10449714
14	Gavin A C, Superti-Furga G (2003). Protein complexes and proteome organization from yeast to man. Curr Opin Chem Biol , 7(1): 21–27 doi: 10.1016/S1367-5931(02)00007-8 pmid:12547422
15	Gerken T A, Tep C, Rarick J (2004). Role of peptide sequence and neighboring residue glycosylation on the substrate specificity of the uridine 5′-diphosphate-alpha-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferases T1 and T2: kinetic modeling of the porcine and canine submaxillary gland mucin tandem repeats. Biochemistry , 43(30): 9888–9900 doi: 10.1021/bi049178e pmid:15274643
16	Griendling K K, Alexander R W (1993). The angiotensin (AT1) receptor. Semin Nephrol , 13(6): 558–566 pmid:8278689
17	Hansen J L, Hauns? S, Brann M R, Sheikh S P, Weiner D M (2004). Loss-of-function polymorphic variants of the human angiotensin II type 1 receptor. Mol Pharmacol , 65(3): 770–777 doi: 10.1124/mol.65.3.770 pmid:14978256
18	Hekkelman M L, Te Beek T A H, Pettifer S R, Thorne D, Attwood T K, Vriend G (2010). WIWS: a protein structure bioinformatics Web service collection. Nucleic Acids Res , 38(Web Server Web Server issue): W719-23 doi: 10.1093/nar/gkq453 pmid:20501602
19	Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank G D, Eguchi S (2007). Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. Clin Sci (Lond) , 112(8): 417–428 doi: 10.1042/CS20060342 pmid:17346243
20	Hogg P J (2003). Disulfide bonds as switches for protein function. Trends Biochem Sci , 28(4): 210–214 doi: 10.1016/S0968-0004(03)00057-4 pmid:12713905
21	Hubbard T J P, Aken B L, Ayling S, Ballester B, Beal K, Bragin E, Brent S, Chen Y, Clapham P, Clarke L, Coates G, Fairley S, Fitzgerald S, Fernandez-Banet J, Gordon L, Graf S, Haider S, Hammond M, Holland R, Howe K, Jenkinson A, Johnson N, Kahari A, Keefe D, Keenan S, Kinsella R, Kokocinski F, Kulesha E, Lawson D, Longden I, Megy K, Meidl P, Overduin B, Parker A, Pritchard B, Rios D, Schuster M, Slater G, Smedley D, Spooner W, Spudich G, Trevanion S, Vilella A, Vogel J, White S, Wilder S, Zadissa A, Birney E, Cunningham F, Curwen V, Durbin R, Fernandez-Suarez X M, Herrero J, Kasprzyk A, Proctor G, Smith J, Searle S, Flicek P (2009). Ensembl 2009. Nucleic Acids Res , 37(Database Database issue): D690–D697 doi: 10.1093/nar/gkn828 pmid:19033362
22	Jeffrey G A, Saenger W (1991) Hydrogen Bonding in Biological Structure. Springer-Verlag, Berlin, Heidelberg , 459–486
23	Johnson M M, Houck J, Chen C (2005). Screening for deleterious non synonymous single-nucleotide polymorphisms in genes involved in steroid hormone metabolism and response. Cancer Epidemiol Biomarkers Prev , 4(5): 1326–1329 doi: 10.1158/1055-9965.EPI-04-0815
24	Karchin R, Diekhans M, Kelly L, Thomas D J, Pieper U, Eswar N, Haussler D, Sali A (2005). LS-SNP: large-scale annotation of coding non-synonymous SNPs based on multiple information sources. Bioinformatics , 21(12): 2814–2820 doi: 10.1093/bioinformatics/bti442 pmid:15827081
25	Khan S, Vihinen M (2007). Spectrum of disease-causing mutations in protein secondary structures. BMC Struct Biol , 7(1): 56 doi: 10.1186/1472-6807-7-56 pmid:17727703
26	Kuhn R M, Karolchik D, Zweig A S, Trumbower H, Thomas D J, Thakkapallayil A, Sugnet C W, Stanke M, Smith K E, Siepel A K, Rosenbloom K R, Rhead B, Raney B J, Pohl A, Pedersen J S, Hsu F, Hinrichs A S, Harte R A, Diekhans M, Clawson H, Bejerano G, Barber G P, Baertsch R, Haussler D, Kent W J (2007). The UCSC genome browser database: update 2007. Nucleic Acids Res , 35(Database Database issue): D668–D673 doi: 10.1093/nar/gkl928 pmid:17142222
27	Lanver D, Mendoza-Mendoza A, Brachmann A, Kahmann R (2010). Sho1 and Msb2-related proteins regulate appressorium development in the smut fungus Ustilago maydis. Plant Cell , 22(6): 2085–2101 doi: 10.1105/tpc.109.073734 pmid:20587773
28	Leclerc P C, Lanctot P M, Auger-Messier M, Escher E, Leduc R, Guillemette G (2006). S-nitrosylation of cysteine 289 of the AT1 receptor decreases its binding affinity for angiotensin II. Br J Pharmacol , 148(3): 306–313 doi: 10.1038/sj.bjp.0706725 pmid:16565729
29	Lee P H, Shatkay H (2008). F-SNP: computationally predicted functional SNPs for disease association studies. Nucleic Acids Res , 36(Database Database issue): D820–D824 doi: 10.1093/nar/gkm904 pmid:17986460
30	Lee P H, Shatkay H (2009). An integrative scoring system for ranking SNPs by their potential deleterious effects. Bioinformatics , 25(8): 1048–1055 doi: 10.1093/bioinformatics/btp103 pmid:19228803
31	Maekawa M, Kikuchi J, Kotani K, Nagao K, Odgerel T, Ueda K, Kawano M, Furukawa Y, Sakurabayashi I (2009). A novel missense mutation of ABCA1 in transmembrane alpha-helix in a Japanese patient with Tangier disease. Atherosclerosis , 206(1): 216–222 doi: 10.1016/j.atherosclerosis.2009.02.018 pmid:19344898
32	Mah J T L, Low E S H, Lee E (2011). In silico SNP analysis and bioinformatics tools: a review of the state of the art to aid drug discovery. Drug Discov Today , 16(17-18): 800–809 doi: 10.1016/j.drudis.2011.07.005 pmid:21803170
33	Meyer M, Wilson P, Schomburg D (1996). Hydrogen bonding and molecular surface shape complementarity as a basis for protein docking. J Mol Biol , 264(1): 199–210 doi: 10.1006/jmbi.1996.0634 pmid:8950278
34	Ng P C, Henikoff S (2003). SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res , 31(13): 3812–3814 doi: 10.1093/nar/gkg509 pmid:12824425
35	Perodin J, Dera?t M, Auger-Messier M, Boucard A A, Rihakova L, Beaulieu M E, Lavigne P, Parent J L, Guillemette G, Leduc R, Escher E (2002). Residues 293 and 294 are ligand contact points of the human angiotensin type 1 receptor. Biochemistry , 41(48): 14348–14356 doi: 10.1021/bi0258602 pmid:12450401
36	Ramensky V, Bork P, Sunyaev S (2002). Human non-synonymous SNPs: server and survey. Nucleic Acids Res , 30(17): 3894–3900 doi: 10.1093/nar/gkf493 pmid:12202775
37	Reumers J, Maurer-Stroh S, Schymkowitz J, Rousseau F (2006). SNPeffect v2.0: a new step in investigating the molecular phenotypic effects of human non-synonymous SNPs. Bioinformatics , 22(17): 2183–2185 doi: 10.1093/bioinformatics/btl348 pmid:16809394
38	Reumers J, Schymkowitz J, Ferkinghoff-Borg J, Stricher F, Serrano L, Rousseau F (2005). SNPeffect: a database mapping molecular phenotypic effects of human non-synonymous coding SNPs. Nucleic Acids Res , 33(Database issue): D527–D532 doi: 10.1093/nar/gki086 pmid:15608254
39	Reynolds C A, Hong M G, Eriksson U K, Blennow K, Bennet A M, Johansson B, Malmberg B, Berg S, Wiklund F, Gatz M, Pedersen N L, Prince J A (2009). A survey of ABCA1 sequence variation confirms association with dementia. Hum Mutat , 30(9): 1348–1354 doi: 10.1002/humu.21076 pmid:19606474
40	Rosskopf D, Schürks M, Rimmbach C, Sch?fers R (2007). Genetics of arterial hypertension and hypotension. Naunyn Schmiedebergs Arch Pharmacol , 374(5-6): 429–469 doi: 10.1007/s00210-007-0133-2 pmid:17262198
41	Rout C C, Rocke D A, Levin J, Gouws E, Reddy D (1993). A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology , 79(2): 262–269 doi: 10.1097/00000542-199308000-00011 pmid:8192733
42	Ryan M, Diekhans M, Lien S, Liu Y, Karchin R (2009). LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures. Bioinformatics , 25(11): 1431–1432 doi: 10.1093/bioinformatics/btp242 pmid:19369493
43	Satija R, Hein J, Lunter G A (2010). Genome-wide functional element detection using pairwise statistical alignment outperforms multiple genome footprinting techniques. Bioinformatics , 26(17): 2116–2120 doi: 10.1093/bioinformatics/btq360 pmid:20610610
44	Siepel A, Bejerano G, Pedersen J S, Hinrichs A S, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier L W, Richards S, Weinstock G M, Wilson R K, Gibbs R A, Kent W J, Miller W, Haussler D (2005). Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res , 15(8): 1034–1050 doi: 10.1101/gr.3715005 pmid:16024819
45	Smith P J, Zhang C, Wang J, Chew S L, Zhang M Q, Krainer A R (2006). An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum Mol Genet , 15(16): 2490–2508 doi: 10.1093/hmg/ddl171 pmid:16825284
46	Sugaya T, Nishimatsu S I, Tanimoto K, Takimoto E, Yamagishi T, Imamura K, Goto S, Imaizumi K, Hisada Y, Otsuka A, Sugiura M, Fukuta K, Fukamizu A, Murakami K (1995). Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem , 270(32): 18719–18722 doi: 10.1074/jbc.270.32.18719 pmid:7642517
47	Sugiyama F, Yagami K, Paigen B (2001). Mouse models of blood pressure regulation and hypertension. Curr Hypertens Rep , 3(1): 41–48 doi: 10.1007/s11906-001-0077-8 pmid:11177707
48	Tobin M D, Tomaszewski M, Braund P S, Hajat C, Raleigh S M, Palmer T M, Caulfield M, Burton P R, Samani N J (2008). Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population. Hypertension , 51(6): 1658–1664 doi: 10.1161/HYPERTENSIONAHA.108.112664 pmid:18443236
49	Viklund H, Granseth E, Elofsson A (2006). Structural classification and prediction of reentrant regions in α-helical transmembrane proteins: application to complete genomes. J Mol Biol , 361(3): 591–603 doi: 10.1016/j.jmb.2006.06.037 pmid:16860824
50	Wetzel R (1987). Harnessing disulfide-bonds using protein engineering. Trends Biochem Sci , 12: 478–482 doi: 10.1016/0968-0004(87)90234-9
51	Wheeler D L, Church D M, Lash A E, Leipe D D, Madden T L, Pontius J U, Schuler G D, Schriml L M, Tatusova T A, Wagner L, Rapp B A, Geer L Y, Helmberg W, Kapustin Y, Khovayko O, Landsman D, Lipman D J, Madden T L, Maglott D R, Miller V, Ostell J, Pruitt K D, Schuler G D, Shumway M, Sequeira E, Sherry S T, Sirotkin K, Souvorov A, Starchenko G, Tatusov R L, Tatusova T A, Wagner L, Yaschenko E (2002). Database resources of the National Center for Biotechnology Information: 2002 update. Nucleic Acids Res , 30(1): 13–16 doi: 10.1093/nar/30.1.13 pmid:11752242
52	Xi H (2002). Linkage analysis on chromosome 2 in essential hypotension pedigrees. Chin Sci Bull , 47(18): 1538–1540 doi: 10.1360/02tb9338
53	Xu D, Tsai C J, Nussinov R (1997). Hydrogen bonds and salt bridges across protein-protein interfaces. Protein Eng , 10(9): 999–1012 doi: 10.1093/protein/10.9.999 pmid:9464564
54	Yuan Z Q, Gottlieb B, Beitel L K, Wong N, Gordon P H, Wang Q, Puisieux A, Foulkes W D, Trifiro M (2002). Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms. Hum Mutat , 19(2): 108–113 doi: 10.1002/humu.10040 pmid:11793469
55	Yue P, Melamud E, Moult J (2006). SNPs3D: candidate gene and SNP selection for association studies. BMC Bioinformatics , 7(1): 166–181 doi: 10.1186/1471-2105-7-166 pmid:16551372
56	Zhang X H F, Kangsamaksin T, Chao M S P, Banerjee J K, Chasin L A (2005). Exon inclusion is dependent on predictable exonic splicing enhancers. Mol Cell Biol , 25(16): 7323–7332 doi: 10.1128/MCB.25.16.7323-7332.2005 pmid:16055740
57	Zhu Y, Hoffman A, Wu X, Zhang H, Zhang Y, Leaderer D, Zheng T (2008). Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools. Mutat Res , 639(1-2): 80–88 doi: 10.1016/j.mrfmmm.2007.11.005 pmid:18191955

[1]	Hansa Jain. *Inhibition and attenuation of pathogenicity of Porphyromonas gingivalis* by leupeptin: A review**[J]. Front. Biol., 2017, 12(3): 192-198.
[2]	YU Yangsheng, BAI Gang, LIU Chunqin, LI Yang, JIN Yongjie, YANG Wenbo. Cloning, expression and characterization of L-cysteine desulfhydrase gene from Pseudomonas sp. TS1138[J]. Front. Biol., 2007, 2(4): 391-396.
[3]	Wu Yu, Wang Jihong, Cui Xiuyun, Zhao Peng, Xu Yuefei, Zhao Baochang. Anti-oxidative effect of ribonuclease inhibitor by site-directed mutagenesis and expression in Pichia pastoris[J]. Front. Biol., 2006, 1(2): 99-103.

Viewed

Full text

Abstract

Cited

Shared

Discussed