EzCatDB: D00438

DB codeD00438
RLCP classification1.13.200.966
CATH domainDomain 12.40.70.10Catalytic domain
Domain 22.40.70.10Catalytic domain
E.C.3.4.23.15
CSA1bbs,1rne

CATH domainRelated DB codes (homologues)
2.40.70.10D00471,D00436,D00439,D00440,D00441,D00442,D00443,D00437,D00444,D00423,D00445,D00484,M00206,M00166,D00231,D00529

Enzyme Name
Swiss-protKEGG

P00796P00797
Protein nameRenin-2Reninrenin
angiotensin-forming enzyme
angiotensinogenase
SynonymsEC 3.4.23.15
Angiotensinogenase
Submandibular gland renin
EC 3.4.23.15
Angiotensinogenase
ContainsRenin-2 heavy chain
Renin-2 light chain
None


Swiss-prot:Accession NumberP00796P00797
Entry nameRENI2_MOUSERENI_HUMAN
ActivityCleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I.Cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I.
SubunitDimer of a heavy chain and a light chain joined by a disulfide bond.Interacts with ATP6AP2.
Subcellular locationSecreted.Secreted. Membrane. Note=Associated to membranes via binding to ATP6AP2.
Cofactor



SubstratesProductsintermediates
KEGG-idC02246C00001C00873I00136
CompoundAngiotensinogenH2OAngiotensin IAmino-diol-tetrahedral intermediate
Typepeptide/proteinH2Oamino acids,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,imine group,lipid,peptide/protein
1bbsA01Unbound
UnboundUnbound
1bilA01Analogue:0IU
UnboundUnbound
1bilB01Analogue:0IU
UnboundUnbound
1bimA01Analogue:0QB
UnboundUnbound
1bimB01Analogue:0QB
UnboundUnbound
1hrnA01Analogue:03D
UnboundUnbound
1hrnB01Analogue:03D
UnboundUnbound
1rneA01Unbound
UnboundTransition-state-analogue:C60
1smrA01Unbound
UnboundTransition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain B)
1smrC01Unbound
UnboundTransition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain D)
1smrE01Unbound
UnboundTransition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain F)
1smrG01Unbound
UnboundTransition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain H)
2renA01Unbound
UnboundUnbound
1bbsA02Unbound
UnboundUnbound
1bilA02Unbound
UnboundUnbound
1bilB02Unbound
UnboundUnbound
1bimA02Unbound
UnboundUnbound
1bimB02Unbound
UnboundUnbound
1hrnA02Unbound
UnboundUnbound
1hrnB02Unbound
UnboundUnbound
1rneA02Unbound
UnboundUnbound
1smrA02Unbound
UnboundUnbound
1smrC02Unbound
UnboundUnbound
1smrE02Unbound
UnboundUnbound
1smrG02Unbound
UnboundUnbound
2renA02Unbound
UnboundUnbound

Active-site residues
resource
Swiss-prot;P00796, P00797
pdbCatalytic residues
1bbsA01ASP 32
1bilA01ASP 32
1bilB01ASP 32
1bimA01ASP 32
1bimB01ASP 32
1hrnA01ASP 32
1hrnB01ASP 32
1rneA01ASP 32
1smrA01ASP 32
1smrC01ASP 32
1smrE01ASP 32
1smrG01ASP 32
2renA01ASP 38
1bbsA02ASP 215
1bilA02ASP 215
1bilB02ASP 215
1bimA02ASP 215
1bimB02ASP 215
1hrnA02ASP 215
1hrnB02ASP 215
1rneA02ASP 215
1smrA02ASP 215
1smrC02ASP 215
1smrE02ASP 215
1smrG02ASP 215
2renA02ASP 226

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.273
[8]Fig.5, p.7010-7012
[22]p.469

references
[1]
PubMed ID5062188
JournalAnal Biochem
Year1972
Volume45
Pages374-86
AuthorsOntjes DA, Majstoravich J Jr, Roberts JC
TitleRadiochemical assay for renin utilizing a synthetic insoluble substrate.
[2]
PubMed ID6346109
JournalNature
Year1983
Volume304
Pages273-5
AuthorsBlundell T, Sibanda BL, Pearl L
TitleThree-dimensional structure, specificity and catalytic mechanism of renin.
[3]
PubMed ID6432579
JournalFEBS Lett
Year1984
Volume174
Pages102-11
AuthorsSibanda BL, Blundell T, Hobart PM, Fogliano M, Bindra JS, Dominy BW, Chirgwin JM
TitleComputer graphics modelling of human renin. Specificity, catalytic activity and intron-exon junctions.
[4]
PubMed ID6397583
JournalJ Pharmacobiodyn
Year1984
Volume7
Pages820-9
AuthorsMorimoto S, Ito K, Iwamoto T, Koseda Y, Takaoka M
TitleConversion of low molecular weight renin into the high molecular weight form by Cu2+ in the rat kidney.
[5]
PubMed ID3912234
JournalBiochem Soc Trans
Year1985
Volume13
Pages1036-41
AuthorsHemmings AM, Foundling SI, Sibanda BL, Wood SP, Pearl LH, Blundell T
TitleEnergy calculations on aspartic proteinases: human renin, endothiapepsin and its complex with an angiotensinogen fragment analogue, H-142.
[6]
PubMed ID3312053
JournalInt J Pept Protein Res
Year1987
Volume30
Pages44-53
AuthorsRoy P, Delepierre M, Wagnon J, Nisato D, Roques BP
TitleConformational analysis of pepstatin and related renin inhibitors by 400 MHz 1H n.m.r. spectroscopy.
[7]
PubMed ID2485071
JournalJ Cardiovasc Pharmacol
Year1987
Volume10 Suppl 7
PagesS91-3
AuthorsCarlson WD, Handschumacher M, Summers N, Karplus M, Haber E
TitleModels for the three-dimensional structure of renin inhibitors bound in the active site of human renin: an analysis of the properties that produce tight binding.
[8]
PubMed ID3313384
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages7009-13
AuthorsSuguna K, Padlan EA, Smith CW, Carlson WD, Davies DR
TitleBinding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
[9]
PubMed ID3046663
JournalBiochemistry
Year1988
Volume27
Pages4071-8
AuthorsFehrentz JA, Heitz A, Seyer R, Fulcrand P, Devilliers R, Castro B, Heitz F, Carelli C
TitlePeptides mimicking the flap of human renin: synthesis, conformation, and antibody recognition.
[10]
PubMed ID3143009
JournalJ Med Chem
Year1988
Volume31
Pages2264-76
AuthorsLuly JR, BaMaung N, Soderquist J, Fung AK, Stein H, Kleinert HD, Marcotte PA, Egan DA, Bopp B, Merits I, et al
TitleRenin inhibitors. Dipeptide analogues of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency.
[11]
PubMed ID2655734
JournalBiopolymers
Year1989
Volume28
Pages41-9
AuthorsPrecigoux G, Benkoulouche M, Geoffre S
TitleThe renin-angiotensin system: an example of the study of linear peptides by x-ray crystallography.
[12]
PubMed ID2661711
JournalJ Clin Chem Clin Biochem
Year1989
Volume27
Pages201-4
AuthorsHigaki J, Morishita R, Ogihara T
TitleMeasurements of enzyme activity and immunoreactivity of plasma renin. Limitations of the conventional method for assay of plasma renin catalytic activity.
[13]
PubMed ID2666620
JournalJ Hypertens Suppl
Year1989
Volume7
PagesS9-14
AuthorsMorris BJ
TitleHuman renin protein and gene structures: present and future targets for renin blockade in treatment of hypertension.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID89162064
PubMed ID2493678
JournalScience
Year1989
Volume243
Pages1346-51
AuthorsSielecki AR, Hayakawa K, Fujinaga M, Murphy ME, Fraser M, Muir AK, Carilli CT, Lewicki JA, Baxter JD, James MN
TitleStructure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 A resolution.
Related PDB2ren
Related Swiss-protP00797
[15]
PubMed ID2100004
JournalPhysiol Chem Phys Med NMR
Year1990
Volume22
Pages105-13
AuthorsSrivastava S, Phadke RS, Govil G
TitleSolvent induced conformational changes in renin inhibitor polypeptide.
[16]
PubMed ID1888732
JournalBiochemistry
Year1991
Volume30
Pages8717-21
AuthorsZhang ZY, Reardon IM, Hui JO, O'Connell KL, Poorman RA, Tomasselli AG, Heinrikson RL
TitleZinc inhibition of renin and the protease from human immunodeficiency virus type 1.
[17]
PubMed ID2002469
JournalJ Med Chem
Year1991
Volume34
Pages887-900
AuthorsWilliams PD, Perlow DS, Payne LS, Holloway MK, Siegl PK, Schorn TW, Lynch RJ, Doyle JJ, Strouse JF, Vlasuk GP, et al
TitleRenin inhibitors containing conformationally restricted P1-P1' dipeptide mimetics.
[18]
CommentsX-ray crystallography
PubMed ID1807356
JournalJ Struct Biol
Year1991
Volume107
Pages227-36
AuthorsRahuel J, Priestle JP, Grutter MG
TitleThe crystal structures of recombinant glycosylated human renin alone and in complex with a transition state analog inhibitor.
Related PDB1rne
[19]
PubMed ID1587361
JournalFEBS Lett
Year1992
Volume302
Pages97-103
AuthorsReily MD, Thanabal V, Lunney EA, Repine JT, Humblet CC, Wagner G
TitleDesign, synthesis and solution structure of a renin inhibitor. Structural constraints from NOE, and homonuclear and heteronuclear coupling constants combined with distance geometry calculations.
[20]
PubMed ID1601850
JournalJ Biol Chem
Year1992
Volume267
Pages11753-9
AuthorsPitarresi TM, Rubattu S, Heinrikson R, Sealey JE
TitleReversible cryoactivation of recombinant human prorenin.
[21]
PubMed ID1548675
JournalJ Med Chem
Year1992
Volume35
Pages833-46
Authorsde Laszlo SE, Bush BL, Doyle JJ, Greenlee WJ, Hangauer DG, Halgren TA, Lynch RJ, Schorn TW, Siegl PK
TitleSynthesis and use of 3-amino-4-phenyl-2-piperidones and 4-amino-2-benzazepin-3-ones as conformationally restricted phenylalanine isosteres in renin inhibitors.
[22]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID92301530
PubMed ID1608447
JournalNature
Year1992
Volume357
Pages466-72
AuthorsDhanaraj V, Dealwis CG, Frazao C, Badasso M, Sibanda BL, Tickle IJ, Cooper JB, Driessen HP, Newman M, Aguilar C, et al
TitleX-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins.
Related PDB1bbs
Related Swiss-protP00796,P00797
[23]
PubMed ID8107115
JournalJ Mol Biol
Year1994
Volume236
Pages342-60
AuthorsDealwis CG, Frazao C, Badasso M, Cooper JB, Tickle IJ, Driessen H, Blundell TL, Murakami K, Miyazaki H, Sueiras-Diaz J, et al
TitleX-ray analysis at 2.0 A resolution of mouse submaxillary renin complexed with a decapeptide inhibitor CH-66, based on the 4-16 fragment of rat angiotensinogen.
Related PDB1smr
[24]
PubMed ID8540315
JournalAdv Exp Med Biol
Year1995
Volume362
Pages155-66
AuthorsAguilar CF, Dhanaraj V, Guruprasad K, Dealwis C, Badasso M, Cooper JB, Wood SP, Blundell TL
TitleComparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
[25]
PubMed ID8540369
JournalAdv Exp Med Biol
Year1995
Volume362
Pages543-7
AuthorsPitts JE, Crawford MD, Nugent PG, Wester RT, Cooper JB, Mantyla A, Fagerstrom R, Nevalainen H
TitleThe three-dimensional X-ray crystal structure of the aspartic proteinase native to Trichoderma reesei complexed with a renin inhibitor CP-80794.
[26]
PubMed ID9072333
JournalClin Exp Pharmacol Physiol Suppl
Year1995
Volume22
PagesS15-4
AuthorsSuzuki F, Tosaki I, Shiratori Y, Nagai M, Murakami K, Nakamura Y
TitleA role of lysine-43 in the inactivation of rat prorenin.
[27]
PubMed ID7584919
JournalHypertens Res
Year1995
Volume18
Pages131-6
AuthorsShinagawa T, Nakayama K, Uchiyama Y, Kominami E, Doi Y, Hashiba K, Yano K, Hsueh WA, Murakami K
TitleRole of cathepsin B as prorenin processing enzyme in human kidney.
[28]
CommentsX-ray crystallography
PubMed ID7493993
JournalJ Biol Chem
Year1995
Volume270
Pages29520-4
AuthorsTong L, Pav S, Lamarre D, Simoneau B, Lavallee P, Jung G
TitleCrystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors.
Related PDB1bil,1bim
[29]
CommentsX-ray crystallography
PubMed ID7608971
JournalJ Mol Biol
Year1995
Volume250
Pages211-22
AuthorsTong L, Pav S, Lamarre D, Pilote L, LaPlante S, Anderson PC, Jung G
TitleHigh resolution crystal structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors.
Related PDB1hrn
[30]
PubMed ID8956073
JournalInt J Pept Protein Res
Year1996
Volume48
Pages401-10
AuthorsLaplante SR, Tong L, Aubry N, Pav S, Jung G, Anderson PC
TitleSeveral polyhydroxymonoamide renin inhibitors assume similar conformations in the unbound and renin-bound states.
[31]
PubMed ID9561243
JournalAdv Exp Med Biol
Year1998
Volume436
Pages363-73
AuthorsSilva AM, Lee AY, Erickson JW, Goldberg DE
TitleStructural analysis of plasmepsin II. A comparison with human aspartic proteases.
[32]
PubMed ID9781693
JournalFEBS Lett
Year1998
Volume436
Pages267-70
AuthorsStreatfeild-James RM, Williamson D, Pike RN, Tewksbury D, Carrell RW, Coughlin PB
TitleAngiotensinogen cleavage by renin: importance of a structurally constrained N-terminus.
[33]
PubMed ID10427707
JournalBiosci Biotechnol Biochem
Year1999
Volume63
Pages1143-5
AuthorsNasir UM, Suzuki F, Nagai T, Nakagawa T, Nakamura Y
TitleTyrosine-83 of human renin contributes to biphasic pH dependence of the renin-angiotensinogen reaction.
[34]
PubMed ID10903938
JournalChem Biol
Year2000
Volume7
Pages493-504
AuthorsRahuel J, Rasetti V, Maibaum J, Rueger H, Goschke R, Cohen NC, Stutz S, Cumin F, Fuhrer W, Wood JM, Grutter MG
TitleStructure-based drug design: the discovery of novel nonpeptide orally active inhibitors of human renin.
[35]
PubMed ID11926999
JournalJ Biochem (Tokyo)
Year2002
Volume131
Pages605-10
AuthorsTakahashi S, Ogasawara H, Takahashi K, Hori K, Saito K, Mori K
TitleIdentification of a domain conferring nucleotide binding to the N-acetyl-d-glucosamine 2-epimerase (Renin binding protein).
[36]
PubMed ID12927775
JournalBiochem Biophys Res Commun
Year2003
Volume308
Pages698-705
AuthorsWood JM, Maibaum J, Rahuel J, Grutter MG, Cohen NC, Rasetti V, Ruger H, Goschke R, Stutz S, Fuhrer W, Schilling W, Rigollier P, Yamaguchi Y, Cumin F, Baum HP, Schnell CR, Herold P, Mah R, Jensen C, O'Brien E, Stanton A, Bedigian MP
TitleStructure-based design of aliskiren, a novel orally effective renin inhibitor.

comments
This enzyme belongs to the peptidase family-A1.
This enzyme has got a catalytic dyad, composed of two aspartic acid residues, which is the same as that of other aspartate proteases such as pepsin (D00436 in EzCatDB; see [22], [31]). It suggests that it may have a similar reaction mechanism to that of those enzyme.

createdupdated
2004-10-262012-06-27


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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