DB code: D00438

RLCP classification 1.13.200.966 : Hydrolysis
CATH domain 2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
2.40.70.10 : Cathepsin D, subunit A; domain 1 Catalytic domain
E.C. 3.4.23.15
CSA 1bbs 1rne
M-CSA 1bbs 1rne
MACiE

CATH domain Related DB codes (homologues)
2.40.70.10 : Cathepsin D, subunit A; domain 1 D00471 D00436 D00439 D00440 D00441 D00442 D00443 D00437 D00444 D00423 D00445 D00484 M00206 M00166 D00231 D00529

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P00796 Renin-2
EC 3.4.23.15
Angiotensinogenase
Submandibular gland renin
Renin-2 heavy chain
Renin-2 light chain
NP_112470.2 (Protein)
NM_031193.2 (DNA/RNA sequence)
A01.008 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]
P00797 Renin
EC 3.4.23.15
Angiotensinogenase
None NP_000528.1 (Protein)
NM_000537.3 (DNA/RNA sequence)
A01.007 (Aspartic)
PF07966 (A1_Propeptide)
PF00026 (Asp)
[Graphical View]

KEGG enzyme name
renin
angiotensin-forming enzyme
angiotensinogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00796 RENI2_MOUSE Cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I. Dimer of a heavy chain and a light chain joined by a disulfide bond. Secreted.
P00797 RENI_HUMAN Cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I. Interacts with ATP6AP2. Secreted. Membrane. Note=Associated to membranes via binding to ATP6AP2.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C02246 C00001 C00873 I00136
E.C.
Compound Angiotensinogen H2O Angiotensin I Amino-diol-tetrahedral intermediate
Type peptide/protein H2O amino acids,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,imine group,lipid,peptide/protein
ChEBI 15377
 15377
 		2718
 2718
PubChem 22247451
 962
 22247451
 962
 		3081372
 90657349
 3081372
 90657349
1bbsA01 Unbound Unbound Unbound
1bilA01 Analogue:0IU Unbound Unbound
1bilB01 Analogue:0IU Unbound Unbound
1bimA01 Analogue:0QB Unbound Unbound
1bimB01 Analogue:0QB Unbound Unbound
1hrnA01 Analogue:03D Unbound Unbound
1hrnB01 Analogue:03D Unbound Unbound
1rneA01 Unbound Unbound Transition-state-analogue:C60
1smrA01 Unbound Unbound Transition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain B)
1smrC01 Unbound Unbound Transition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain D)
1smrE01 Unbound Unbound Transition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain F)
1smrG01 Unbound Unbound Transition-state-analogue:PIV-HIS-PRO-PHE-HIS-LPL-TYR-TYR-SER(chain H)
2renA01 Unbound Unbound Unbound
1bbsA02 Unbound Unbound Unbound
1bilA02 Unbound Unbound Unbound
1bilB02 Unbound Unbound Unbound
1bimA02 Unbound Unbound Unbound
1bimB02 Unbound Unbound Unbound
1hrnA02 Unbound Unbound Unbound
1hrnB02 Unbound Unbound Unbound
1rneA02 Unbound Unbound Unbound
1smrA02 Unbound Unbound Unbound
1smrC02 Unbound Unbound Unbound
1smrE02 Unbound Unbound Unbound
1smrG02 Unbound Unbound Unbound
2renA02 Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00796, P00797

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bbsA01 ASP 32
1bilA01 ASP 32
1bilB01 ASP 32
1bimA01 ASP 32
1bimB01 ASP 32
1hrnA01 ASP 32
1hrnB01 ASP 32
1rneA01 ASP 32
1smrA01 ASP 32
1smrC01 ASP 32
1smrE01 ASP 32
1smrG01 ASP 32
2renA01 ASP 38
1bbsA02 ASP 215
1bilA02 ASP 215
1bilB02 ASP 215
1bimA02 ASP 215
1bimB02 ASP 215
1hrnA02 ASP 215
1hrnB02 ASP 215
1rneA02 ASP 215
1smrA02 ASP 215
1smrC02 ASP 215
1smrE02 ASP 215
1smrG02 ASP 215
2renA02 ASP 226

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.273
[8]
Fig.5, p.7010-7012
[22]
p.469

References
[1]
Resource
Comments
Medline ID
PubMed ID 5062188
Journal Anal Biochem
Year 1972
Volume 45
Pages 374-86
Authors Ontjes DA, Majstoravich J Jr, Roberts JC
Title Radiochemical assay for renin utilizing a synthetic insoluble substrate.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6346109
Journal Nature
Year 1983
Volume 304
Pages 273-5
Authors Blundell T, Sibanda BL, Pearl L
Title Three-dimensional structure, specificity and catalytic mechanism of renin.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 6432579
Journal FEBS Lett
Year 1984
Volume 174
Pages 102-11
Authors Sibanda BL, Blundell T, Hobart PM, Fogliano M, Bindra JS, Dominy BW, Chirgwin JM
Title Computer graphics modelling of human renin. Specificity, catalytic activity and intron-exon junctions.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 6397583
Journal J Pharmacobiodyn
Year 1984
Volume 7
Pages 820-9
Authors Morimoto S, Ito K, Iwamoto T, Koseda Y, Takaoka M
Title Conversion of low molecular weight renin into the high molecular weight form by Cu2+ in the rat kidney.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3912234
Journal Biochem Soc Trans
Year 1985
Volume 13
Pages 1036-41
Authors Hemmings AM, Foundling SI, Sibanda BL, Wood SP, Pearl LH, Blundell T
Title Energy calculations on aspartic proteinases: human renin, endothiapepsin and its complex with an angiotensinogen fragment analogue, H-142.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 3312053
Journal Int J Pept Protein Res
Year 1987
Volume 30
Pages 44-53
Authors Roy P, Delepierre M, Wagnon J, Nisato D, Roques BP
Title Conformational analysis of pepstatin and related renin inhibitors by 400 MHz 1H n.m.r. spectroscopy.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2485071
Journal J Cardiovasc Pharmacol
Year 1987
Volume 10 Suppl 7
Pages S91-3
Authors Carlson WD, Handschumacher M, Summers N, Karplus M, Haber E
Title Models 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.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 3313384
Journal Proc Natl Acad Sci U S A
Year 1987
Volume 84
Pages 7009-13
Authors Suguna K, Padlan EA, Smith CW, Carlson WD, Davies DR
Title Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 3046663
Journal Biochemistry
Year 1988
Volume 27
Pages 4071-8
Authors Fehrentz JA, Heitz A, Seyer R, Fulcrand P, Devilliers R, Castro B, Heitz F, Carelli C
Title Peptides mimicking the flap of human renin: synthesis, conformation, and antibody recognition.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 3143009
Journal J Med Chem
Year 1988
Volume 31
Pages 2264-76
Authors Luly JR, BaMaung N, Soderquist J, Fung AK, Stein H, Kleinert HD, Marcotte PA, Egan DA, Bopp B, Merits I, et al
Title Renin inhibitors. Dipeptide analogues of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2655734
Journal Biopolymers
Year 1989
Volume 28
Pages 41-9
Authors Precigoux G, Benkoulouche M, Geoffre S
Title The renin-angiotensin system: an example of the study of linear peptides by x-ray crystallography.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 2661711
Journal J Clin Chem Clin Biochem
Year 1989
Volume 27
Pages 201-4
Authors Higaki J, Morishita R, Ogihara T
Title Measurements of enzyme activity and immunoreactivity of plasma renin. Limitations of the conventional method for assay of plasma renin catalytic activity.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 2666620
Journal J Hypertens Suppl
Year 1989
Volume 7
Pages S9-14
Authors Morris BJ
Title Human renin protein and gene structures: present and future targets for renin blockade in treatment of hypertension.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 89162064
PubMed ID 2493678
Journal Science
Year 1989
Volume 243
Pages 1346-51
Authors Sielecki AR, Hayakawa K, Fujinaga M, Murphy ME, Fraser M, Muir AK, Carilli CT, Lewicki JA, Baxter JD, James MN
Title Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 A resolution.
Related PDB 2ren
Related UniProtKB P00797
[15]
Resource
Comments
Medline ID
PubMed ID 2100004
Journal Physiol Chem Phys Med NMR
Year 1990
Volume 22
Pages 105-13
Authors Srivastava S, Phadke RS, Govil G
Title Solvent induced conformational changes in renin inhibitor polypeptide.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 1888732
Journal Biochemistry
Year 1991
Volume 30
Pages 8717-21
Authors Zhang ZY, Reardon IM, Hui JO, O'Connell KL, Poorman RA, Tomasselli AG, Heinrikson RL
Title Zinc inhibition of renin and the protease from human immunodeficiency virus type 1.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 2002469
Journal J Med Chem
Year 1991
Volume 34
Pages 887-900
Authors Williams PD, Perlow DS, Payne LS, Holloway MK, Siegl PK, Schorn TW, Lynch RJ, Doyle JJ, Strouse JF, Vlasuk GP, et al
Title Renin inhibitors containing conformationally restricted P1-P1' dipeptide mimetics.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1807356
Journal J Struct Biol
Year 1991
Volume 107
Pages 227-36
Authors Rahuel J, Priestle JP, Grutter MG
Title The crystal structures of recombinant glycosylated human renin alone and in complex with a transition state analog inhibitor.
Related PDB 1rne
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 1587361
Journal FEBS Lett
Year 1992
Volume 302
Pages 97-103
Authors Reily MD, Thanabal V, Lunney EA, Repine JT, Humblet CC, Wagner G
Title Design, synthesis and solution structure of a renin inhibitor. Structural constraints from NOE, and homonuclear and heteronuclear coupling constants combined with distance geometry calculations.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 1601850
Journal J Biol Chem
Year 1992
Volume 267
Pages 11753-9
Authors Pitarresi TM, Rubattu S, Heinrikson R, Sealey JE
Title Reversible cryoactivation of recombinant human prorenin.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 1548675
Journal J Med Chem
Year 1992
Volume 35
Pages 833-46
Authors de Laszlo SE, Bush BL, Doyle JJ, Greenlee WJ, Hangauer DG, Halgren TA, Lynch RJ, Schorn TW, Siegl PK
Title Synthesis and use of 3-amino-4-phenyl-2-piperidones and 4-amino-2-benzazepin-3-ones as conformationally restricted phenylalanine isosteres in renin inhibitors.
Related PDB
Related UniProtKB
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 92301530
PubMed ID 1608447
Journal Nature
Year 1992
Volume 357
Pages 466-72
Authors Dhanaraj V, Dealwis CG, Frazao C, Badasso M, Sibanda BL, Tickle IJ, Cooper JB, Driessen HP, Newman M, Aguilar C, et al
Title X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins.
Related PDB 1bbs
Related UniProtKB P00796 P00797
[23]
Resource
Comments
Medline ID
PubMed ID 8107115
Journal J Mol Biol
Year 1994
Volume 236
Pages 342-60
Authors Dealwis CG, Frazao C, Badasso M, Cooper JB, Tickle IJ, Driessen H, Blundell TL, Murakami K, Miyazaki H, Sueiras-Diaz J, et al
Title X-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 PDB 1smr
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 8540315
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 155-66
Authors Aguilar CF, Dhanaraj V, Guruprasad K, Dealwis C, Badasso M, Cooper JB, Wood SP, Blundell TL
Title Comparisons of the three-dimensional structures, specificities and glycosylation of renins, yeast proteinase A and cathepsin D.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 8540369
Journal Adv Exp Med Biol
Year 1995
Volume 362
Pages 543-7
Authors Pitts JE, Crawford MD, Nugent PG, Wester RT, Cooper JB, Mantyla A, Fagerstrom R, Nevalainen H
Title The three-dimensional X-ray crystal structure of the aspartic proteinase native to Trichoderma reesei complexed with a renin inhibitor CP-80794.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 9072333
Journal Clin Exp Pharmacol Physiol Suppl
Year 1995
Volume 22
Pages S15-4
Authors Suzuki F, Tosaki I, Shiratori Y, Nagai M, Murakami K, Nakamura Y
Title A role of lysine-43 in the inactivation of rat prorenin.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 7584919
Journal Hypertens Res
Year 1995
Volume 18
Pages 131-6
Authors Shinagawa T, Nakayama K, Uchiyama Y, Kominami E, Doi Y, Hashiba K, Yano K, Hsueh WA, Murakami K
Title Role of cathepsin B as prorenin processing enzyme in human kidney.
Related PDB
Related UniProtKB
[28]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7493993
Journal J Biol Chem
Year 1995
Volume 270
Pages 29520-4
Authors Tong L, Pav S, Lamarre D, Simoneau B, Lavallee P, Jung G
Title Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors.
Related PDB 1bil 1bim
Related UniProtKB
[29]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7608971
Journal J Mol Biol
Year 1995
Volume 250
Pages 211-22
Authors Tong L, Pav S, Lamarre D, Pilote L, LaPlante S, Anderson PC, Jung G
Title High resolution crystal structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors.
Related PDB 1hrn
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 8956073
Journal Int J Pept Protein Res
Year 1996
Volume 48
Pages 401-10
Authors Laplante SR, Tong L, Aubry N, Pav S, Jung G, Anderson PC
Title Several polyhydroxymonoamide renin inhibitors assume similar conformations in the unbound and renin-bound states.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 9561243
Journal Adv Exp Med Biol
Year 1998
Volume 436
Pages 363-73
Authors Silva AM, Lee AY, Erickson JW, Goldberg DE
Title Structural analysis of plasmepsin II. A comparison with human aspartic proteases.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 9781693
Journal FEBS Lett
Year 1998
Volume 436
Pages 267-70
Authors Streatfeild-James RM, Williamson D, Pike RN, Tewksbury D, Carrell RW, Coughlin PB
Title Angiotensinogen cleavage by renin: importance of a structurally constrained N-terminus.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 10427707
Journal Biosci Biotechnol Biochem
Year 1999
Volume 63
Pages 1143-5
Authors Nasir UM, Suzuki F, Nagai T, Nakagawa T, Nakamura Y
Title Tyrosine-83 of human renin contributes to biphasic pH dependence of the renin-angiotensinogen reaction.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 10903938
Journal Chem Biol
Year 2000
Volume 7
Pages 493-504
Authors Rahuel J, Rasetti V, Maibaum J, Rueger H, Goschke R, Cohen NC, Stutz S, Cumin F, Fuhrer W, Wood JM, Grutter MG
Title Structure-based drug design: the discovery of novel nonpeptide orally active inhibitors of human renin.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 11926999
Journal J Biochem (Tokyo)
Year 2002
Volume 131
Pages 605-10
Authors Takahashi S, Ogasawara H, Takahashi K, Hori K, Saito K, Mori K
Title Identification of a domain conferring nucleotide binding to the N-acetyl-d-glucosamine 2-epimerase (Renin binding protein).
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 12927775
Journal Biochem Biophys Res Commun
Year 2003
Volume 308
Pages 698-705
Authors Wood 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
Title Structure-based design of aliskiren, a novel orally effective renin inhibitor.
Related PDB
Related UniProtKB

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.

Created Updated
2004-10-26 2012-06-27