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PDBsum entry 1o86

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
1o86
Jmol
Contents
Protein chain
575 a.a. *
Ligands
GLY
LPR
Metals
_CL ×2
_ZN
Waters ×570
* Residue conservation analysis
PDB id:
1o86
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of human angiotensin converting enzyme in with lisinopril.
Structure: Angiotensin converting enzyme. Chain: a. Fragment: residues 68-656. Synonym: ace-t, dipeptidyl carboxypeptidase i, kininase ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: testis. Expressed in: cricetulus griseus. Expression_system_taxid: 10029
Resolution:
2.00Å     R-factor:   0.180     R-free:   0.220
Authors: R.Natesh,S.L.U.Schwager,E.D.Sturrock,K.R.Acharya
Key ref:
R.Natesh et al. (2003). Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature, 421, 551-554. PubMed id: 12540854 DOI: 10.1038/nature01370
Date:
25-Nov-02     Release date:   07-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12821  (ACE_HUMAN) -  Angiotensin-converting enzyme
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1306 a.a.
575 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.3.4.15.1  - Peptidyl-dipeptidase A.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Xbb, when Xaa is not Pro, and Xbb is neither Asp nor Glu. Converts angiotensin I to angiotensin II.
      Cofactor: Zinc
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     2 terms  

 

 
DOI no: 10.1038/nature01370 Nature 421:551-554 (2003)
PubMed id: 12540854  
 
 
Crystal structure of the human angiotensin-converting enzyme-lisinopril complex.
R.Natesh, S.L.Schwager, E.D.Sturrock, K.R.Acharya.
 
  ABSTRACT  
 
Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Overview of tACE structure. a, Stereo view of the ribbon representation of the molecule looking down on the active site. The molecule can be divided into two portions, as subdomains I and II (cyan and pink, respectively). The active-site zinc ion and the lisinopril molecule are shown in green and yellow, respectively. The two chloride ions are shown as red spheres. b, Molecular surface representation (negative and positive potentials in red and blue, respectively) showing the active-site groove. The view is at 90 (towards the observer) to a. For clarity, the molecular surface has been sliced. The buried lisinopril molecule is shown in yellow. Helices 1, 2 and 3 forming the lid are shown. c, The structure -sequence relationship in tACE^10. The secondary structure elements (subdomain I in cyan; subdomain II in pink) follow the same colour code as in a. , -helices; , -strands; H, 3[10] helices. The important residues that are involved in binding are indicated as follows: zinc ligands, green boxes; chloride-binding residues, orange (Cl1) and red (Cl2) boxes; lisinopril-binding residues, yellow boxes; and glycosylation sites, black boxes.
Figure 2.
Figure 2: Details of the active site. a, Binding of lisinopril to tACE (stereo representation). Selected residues are shown in a 'ball-and-stick' representation with zinc atoms in green, chloride ions in red, water molecules in purple, and lisinopril (inhibitor) in yellow. Important secondary structure elements are marked. The lisinopril, Cl2, water hydrogen bonds and zinc coordination are shown in cyan, red, purple and green dotted lines, respectively. b, Schematic view of lisinopril binding with distances marked in . The different binding subsites are labelled.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 421, 551-554) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21185549 B.Hernández-Ledesma, M.del Mar Contreras, and I.Recio (2011).
Antihypertensive peptides: production, bioavailability and incorporation into foods.
  Adv Colloid Interface Sci, 165, 23-35.  
21186397 B.J.Bhuyan, and G.Mugesh (2011).
Synthesis, characterization and antioxidant activity of angiotensin converting enzyme inhibitors.
  Org Biomol Chem, 9, 1356-1365.  
21470562 D.S.Aragão, T.S.Cunha, D.Y.Arita, M.C.Andrade, A.B.Fernandes, I.K.Watanabe, R.A.Mortara, and D.E.Casarini (2011).
Purification and characterization of angiotensin converting enzyme 2 (ACE2) from murine model of mesangial cell in culture.
  Int J Biol Macromol, 49, 79-84.  
21352096 M.Akif, S.L.Schwager, C.S.Anthony, B.Czarny, F.Beau, V.Dive, E.D.Sturrock, and K.R.Acharya (2011).
Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide.
  Biochem J, 436, 53-59.
PDB codes: 2xy9 2xyd
21328404 V.Hähnke, A.Klenner, F.Rippmann, and G.Schneider (2011).
Pharmacophore alignment search tool: Influence of the third dimension on text-based similarity searching.
  J Comput Chem, 32, 1618-1634.  
19898265 C.F.Thorn, T.E.Klein, and R.B.Altman (2010).
PharmGKB summary: very important pharmacogene information for angiotensin-converting enzyme.
  Pharmacogenet Genomics, 20, 143-146.  
19908272 D.M.Krüger, and A.Evers (2010).
Comparison of structure- and ligand-based virtual screening protocols considering hit list complementarity and enrichment factors.
  ChemMedChem, 5, 148-158.  
20065150 E.G.Erdös, F.Tan, and R.A.Skidgel (2010).
Angiotensin I-converting enzyme inhibitors are allosteric enhancers of kinin B1 and B2 receptor function.
  Hypertension, 55, 214-220.  
20014331 G.A.Dalkas, D.Marchand, J.C.Galleyrand, J.Martinez, G.A.Spyroulias, P.Cordopatis, and F.Cavelier (2010).
Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme.
  J Pept Sci, 16, 91-97.  
20233165 J.M.Watermeyer, W.L.Kröger, H.G.O'Neill, B.T.Sewell, and E.D.Sturrock (2010).
Characterization of domain-selective inhibitor binding in angiotensin-converting enzyme using a novel derivative of lisinopril.
  Biochem J, 428, 67-74.
PDB code: 3l3n
20454656 S.M.Danilov, S.Kalinin, Z.Chen, E.I.Vinokour, A.B.Nesterovitch, D.E.Schwartz, O.Gribouval, M.C.Gubler, and R.D.Minshall (2010).
Angiotensin I-converting enzyme Gln1069Arg mutation impairs trafficking to the cell surface resulting in selective denaturation of the C-domain.
  PLoS One, 5, e10438.  
20030584 X.Sun, B.Rentzsch, M.Gong, J.Eichhorst, K.Pankow, G.Papsdorf, B.Maul, M.Bader, and W.E.Siems (2010).
Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE.
  Biol Chem, 391, 235-244.  
20634989 Z.Spyranti, A.S.Galanis, G.Pairas, G.A.Spyroulias, E.Manessi-Zoupa, and P.Cordopatis (2010).
Synthetic peptides as structural maquettes of Angiotensin-I converting enzyme catalytic sites.
  Bioinorg Chem Appl, (), 820476.  
18816584 A.S.Pina, and A.C.Roque (2009).
Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme.
  J Mol Recognit, 22, 162-168.  
19558329 C.E.Cunha, H.d.e. .F.Magliarelli, T.Paschoalin, A.T.Nchinda, J.C.Lima, M.A.Juliano, P.B.Paiva, E.D.Sturrock, L.R.Travassos, and A.K.Carmona (2009).
Catalytic properties of recombinant dipeptidyl carboxypeptidase from Escherichia coli: a comparative study with angiotensin I-converting enzyme.
  Biol Chem, 390, 931-940.  
19552427 D.Xu, and H.Guo (2009).
Quantum mechanical/molecular mechanical and density functional theory studies of a prototypical zinc peptidase (carboxypeptidase A) suggest a general acid-general base mechanism.
  J Am Chem Soc, 131, 9780-9788.  
19188834 K.Hanif, Snehlata, M.C.Pavar, E.Arif, M.Fahim, M.A.Pasha, and S.Pasha (2009).
Effect of 3-thienylalanine-ornithine-proline, new sulfur-containing angiotensin-converting enzyme inhibitor on blood pressure and oxidative stress in spontaneously hypertensive rats.
  J Cardiovasc Pharmacol, 53, 145-150.  
19685535 L.Hocharoen, and J.A.Cowan (2009).
Metallotherapeutics: novel strategies in drug design.
  Chemistry, 15, 8670-8676.  
19706421 M.Platten, S.Youssef, E.M.Hur, P.P.Ho, M.H.Han, T.V.Lanz, L.K.Phillips, M.J.Goldstein, R.Bhat, C.S.Raine, R.A.Sobel, and L.Steinman (2009).
Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity.
  Proc Natl Acad Sci U S A, 106, 14948-14953.  
18478260 M.Uematsu, O.Sakamoto, T.Ohura, N.Shimizu, K.Satomura, and S.Tsuchiya (2009).
A further case of renal tubular dysgenesis surviving the neonatal period.
  Eur J Pediatr, 168, 207-209.  
19551715 S.S.Vamvakas, L.Leondiadis, G.Pairas, E.Manessi-Zoupa, G.A.Spyroulias, and P.Cordopatis (2009).
Folding in solution of the C-catalytic protein fragment of angiotensin-converting enzyme.
  J Pept Sci, 15, 504-510.  
19307186 X.Liu, C.O.Bellamy, M.A.Bailey, L.J.Mullins, D.R.Dunbar, C.J.Kenyon, G.Brooker, S.Kantachuvesiri, K.Maratou, A.Ashek, A.F.Clark, S.Fleming, and J.J.Mullins (2009).
Angiotensin-converting enzyme is a modifier of hypertensive end organ damage.
  J Biol Chem, 284, 15564-15572.  
18563261 B.M.Liénard, G.Garau, L.Horsfall, A.I.Karsisiotis, C.Damblon, P.Lassaux, C.Papamicael, G.C.Roberts, M.Galleni, O.Dideberg, J.M.Frère, and C.J.Schofield (2008).
Structural basis for the broad-spectrum inhibition of metallo-beta-lactamases by thiols.
  Org Biomol Chem, 6, 2282-2294.
PDB codes: 2qds 2qdt
19021774 C.A.Rushworth, J.L.Guy, and A.J.Turner (2008).
Residues affecting the chloride regulation and substrate selectivity of the angiotensin-converting enzymes (ACE and ACE2) identified by site-directed mutagenesis.
  FEBS J, 275, 6033-6042.  
18539138 C.E.Isaza, X.Zhong, L.E.Rosas, J.D.White, R.P.Chen, G.F.Liang, S.I.Chan, A.R.Satoskar, and M.K.Chan (2008).
A proposed role for Leishmania major carboxypeptidase in peptide catabolism.
  Biochem Biophys Res Commun, 373, 25-29.  
  19727327 D.B.Berkowitz, K.R.Karukurichi, R.de la Salud-Bea, D.L.Nelson, and C.D.McCune (2008).
Use of Fluorinated Functionality in Enzyme Inhibitor Development: Mechanistic and Analytical Advantages.
  J Fluor Chem, 129, 731-742.  
18672685 I.A.Naperova, I.V.Baliasnikova, M.N.Petrov, A.V.Vakhitova, V.V.Evdokimov, S.M.Danilov, and O.A.Kost (2008).
[Characteristics of monoclonal antibody binding with the C domain of human angiotensin converting enzyme]
  Bioorg Khim, 34, 358-364.  
18700874 I.V.Balyasnikova, R.Metzger, F.E.Franke, N.Conrad, H.Towbin, D.E.Schwartz, E.D.Sturrock, and S.M.Danilov (2008).
Epitope mapping of mAbs to denatured human testicular ACE (CD143).
  Tissue Antigens, 72, 354-368.  
18636749 S.Chattopadhyay, G.Karan, I.Sen, and G.C.Sen (2008).
A small region in the angiotensin-converting enzyme distal ectodomain is required for cleavage-secretion of the protein at the plasma membrane.
  Biochemistry, 47, 8335-8341.  
18400032 V.Rioli, B.C.Prezoto, K.Konno, R.L.Melo, C.F.Klitzke, E.S.Ferro, M.Ferreira-Lopes, A.C.Camargo, and F.C.Portaro (2008).
A novel bradykinin potentiating peptide isolated from Bothrops jararacussu venom using catallytically inactive oligopeptidase EP24.15.
  FEBS J, 275, 2442-2454.  
18443752 X.Z.Shen, H.D.Xiao, P.Li, C.X.Lin, S.Billet, D.Okwan-Duodu, J.W.Adams, E.A.Bernstein, Y.Xu, S.Fuchs, and K.E.Bernstein (2008).
New insights into the role of angiotensin-converting enzyme obtained from the analysis of genetically modified mice.
  J Mol Med, 86, 679-684.  
17257685 A.H.Danser, W.W.Batenburg, A.H.van den Meiracker, and S.M.Danilov (2007).
ACE phenotyping as a first step toward personalized medicine for ACE inhibitors. Why does ACE genotyping not predict the therapeutic efficacy of ACE inhibition?
  Pharmacol Ther, 113, 607-618.  
17441908 C.Falciani, L.Lozzi, A.Pini, F.Corti, M.Fabbrini, A.Bernini, B.Lelli, N.Niccolai, and L.Bracci (2007).
Molecular basis of branched peptides resistance to enzyme proteolysis.
  Chem Biol Drug Des, 69, 216-221.  
17251185 E.J.Lim, S.Sampath, J.Coll-Rodriguez, J.Schmidt, K.Ray, and D.W.Rodgers (2007).
Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase.
  J Biol Chem, 282, 9722-9732.
PDB codes: 2o36 2o3e
17294247 I.Schellhammer, and M.Rarey (2007).
TrixX: structure-based molecule indexing for large-scale virtual screening in sublinear time.
  J Comput Aided Mol Des, 21, 223-238.  
17321748 M.L.Hemming, D.J.Selkoe, and W.Farris (2007).
Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid beta-protein metabolism in mouse models of Alzheimer disease.
  Neurobiol Dis, 26, 273-281.  
17722167 M.Losacco, R.Gallerani, M.Gobbetti, F.Minervini, and F.De Leo (2007).
Production of active angiotensin-I converting enzyme inhibitory peptides derived from bovine beta-casein by recombinant DNA technologies.
  Biotechnol J, 2, 1425-1434.  
17597519 M.Rella, J.L.Elliot, T.J.Revett, J.Lanfear, A.Phelan, R.M.Jackson, A.J.Turner, and N.M.Hooper (2007).
Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE.
  BMC Genomics, 8, 194.  
17878751 P.Daull, A.Y.Jeng, and B.Battistini (2007).
Towards triple vasopeptidase inhibitors for the treatment of cardiovascular diseases.
  J Cardiovasc Pharmacol, 50, 247-256.  
16972307 S.S.Vamvakas, L.Leondiadis, G.Pairas, E.Manessi-Zoupa, G.A.Spyroulias, and P.Cordopatis (2007).
Expression, purification, and physicochemical characterization of the N-terminal active site of human angiotensin-I converting enzyme.
  J Pept Sci, 13, 31-36.  
17135201 Y.Wang, K.J.Addess, J.Chen, L.Y.Geer, J.He, S.He, S.Lu, T.Madej, A.Marchler-Bauer, P.A.Thiessen, N.Zhang, and S.H.Bryant (2007).
MMDB: annotating protein sequences with Entrez's 3D-structure database.
  Nucleic Acids Res, 35, D298-D300.  
16955069 B.Turk (2006).
Targeting proteases: successes, failures and future prospects.
  Nat Rev Drug Discov, 5, 785-799.  
17042482 J.M.Watermeyer, B.T.Sewell, S.L.Schwager, R.Natesh, H.R.Corradi, K.R.Acharya, and E.D.Sturrock (2006).
Structure of testis ACE glycosylation mutants and evidence for conserved domain movement.
  Biochemistry, 45, 12654-12663.
PDB codes: 2iul 2iux
17044798 M.R.Ehlers (2006).
Safety issues associated with the use of angiotensin-converting enzyme inhibitors.
  Expert Opin Drug Saf, 5, 739-740.  
16623712 N.D.Jullien, P.Cuniasse, D.Georgiadis, A.Yiotakis, and V.Dive (2006).
Combined use of selective inhibitors and fluorogenic substrates to study the specificity of somatic wild-type angiotensin-converting enzyme.
  FEBS J, 273, 1772-1781.  
16874470 N.H.Gokhale, and J.A.Cowan (2006).
Metallopeptide-promoted inactivation of angiotensin-converting enzyme and endothelin-converting enzyme 1: Toward dual-action therapeutics.
  J Biol Inorg Chem, 11, 937-947.  
16997139 P.J.Meek, Z.Liu, L.Tian, C.Y.Wang, W.J.Welsh, and R.J.Zauhar (2006).
Shape Signatures: speeding up computer aided drug discovery.
  Drug Discov Today, 11, 895-904.  
16606345 P.Redelinghuys, A.T.Nchinda, K.Chibale, and E.D.Sturrock (2006).
Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling.
  Biol Chem, 387, 461-466.  
16403023 R.J.Bingham, V.Dive, S.E.Phillips, A.D.Shirras, and R.E.Isaac (2006).
Structural diversity of angiotensin-converting enzyme.
  FEBS J, 273, 362-373.  
16895474 Z.L.Woodman, S.L.Schwager, P.Redelinghuys, A.J.Chubb, E.L.van der Merwe, M.R.Ehlers, and E.D.Sturrock (2006).
Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties.
  Biol Chem, 387, 1043-1051.  
15883972 A.G.Tzakos, and I.P.Gerothanassis (2005).
Domain-selective ligand-binding modes and atomic level pharmacophore refinement in angiotensin I converting enzyme (ACE) inhibitors.
  Chembiochem, 6, 1089-1103.  
16342948 A.L.McClerren, S.Endsley, J.L.Bowman, N.H.Andersen, Z.Guan, J.Rudolph, and C.R.Raetz (2005).
A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin.
  Biochemistry, 44, 16574-16583.  
16307311 D.J.Kuster, and G.R.Marshall (2005).
Validated ligand mapping of ACE active site.
  J Comput Aided Mol Des, 19, 609-615.  
15665832 G.Kondoh, H.Tojo, Y.Nakatani, N.Komazawa, C.Murata, K.Yamagata, Y.Maeda, T.Kinoshita, M.Okabe, R.Taguchi, and J.Takeda (2005).
Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization.
  Nat Med, 11, 160-166.  
15785205 I.V.Balyasnikova, Z.L.Sun, F.E.Franke, Y.V.Berestetskaya, A.J.Chubb, R.F.Albrecht, E.D.Sturrock, and S.M.Danilov (2005).
Monoclonal antibodies 1B3 and 5C8 as probes for monitoring the integrity of the C-terminal end of soluble angiotensin-converting enzyme.
  Hybridoma (Larchmt), 24, 14-26.  
16008552 J.L.Guy, R.M.Jackson, H.A.Jensen, N.M.Hooper, and A.J.Turner (2005).
Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis.
  FEBS J, 272, 3512-3520.  
16271036 N.A.Moiseeva, P.V.Binevski, I.I.Baskin, V.A.Palyulin, and O.A.Kost (2005).
Role of two chloride-binding sites in functioning of testicular angiotensin-converting enzyme.
  Biochemistry (Mosc), 70, 1167-1172.  
16317474 N.H.Gokhale, and J.A.Cowan (2005).
Inactivation of human angiotensin converting enzyme by copper peptide complexes containing ATCUN motifs.
  Chem Commun (Camb), (), 5916-5918.  
15615692 N.Naqvi, K.Liu, R.M.Graham, and A.Husain (2005).
Molecular basis of exopeptidase activity in the C-terminal domain of human angiotensin I-converting enzyme: insights into the origins of its exopeptidase activity.
  J Biol Chem, 280, 6669-6675.  
15692590 P.Corvol (2005).
ACE sets up fertilization.
  Nat Med, 11, 118-119.  
15702069 S.Mayor (2005).
ACEing GPI release.
  Nat Struct Mol Biol, 12, 107-108.  
15994300 T.Suzuki, K.Ishihara, H.Migaki, K.Ishihara, M.Nagao, Y.Yamaguchi-Iwai, and T.Kambe (2005).
Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells.
  J Biol Chem, 280, 30956-30962.  
15525635 T.Suzuki, K.Ishihara, H.Migaki, W.Matsuura, A.Kohda, K.Okumura, M.Nagao, Y.Yamaguchi-Iwai, and T.Kambe (2005).
Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane.
  J Biol Chem, 280, 637-643.  
15165741 A.J.Turner, J.A.Hiscox, and N.M.Hooper (2004).
ACE2: from vasopeptidase to SARS virus receptor.
  Trends Pharmacol Sci, 25, 291-294.  
15508121 A.S.Galanis, G.A.Spyroulias, G.Pairas, E.Manessi-Zoupa, and P.Cordopatis (2004).
Solid-phase synthesis and conformational properties of angiotensin converting enzyme catalytic-site peptides: the basis for a structural study on the enzyme-substrate interaction.
  Biopolymers, 76, 512-526.  
15337510 D.J.Burinsky, and S.L.Sides (2004).
Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors.
  J Am Soc Mass Spectrom, 15, 1300-1314.  
14998993 K.Ray, C.S.Hines, J.Coll-Rodriguez, and D.W.Rodgers (2004).
Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization.
  J Biol Chem, 279, 20480-20489.
PDB code: 1s4b
15009531 N.Inguimbert, H.Poras, H.Dhotel, F.Beslot, E.Scalbert, C.Bennejean, P.Renard, M.C.Fournié-Zaluski, and B.P.Roques (2004).
In vivo properties of thiol inhibitors of the three vasopeptidases NEP, ACE and ECE are improved by introduction of a 7-azatryptophan in P2' position.
  J Pept Res, 63, 99.  
14754895 P.Towler, B.Staker, S.G.Prasad, S.Menon, J.Tang, T.Parsons, D.Ryan, M.Fisher, D.Williams, N.A.Dales, M.A.Patane, and M.W.Pantoliano (2004).
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.
  J Biol Chem, 279, 17996-18007.
PDB codes: 1r42 1r4l
12767125 A.S.Galanis, G.A.Spyroulias, R.Pierattelli, A.Tzakos, A.Troganis, I.P.Gerothanassis, G.Pairas, E.Manessi-Zoupa, and P.Cordopatis (2003).
Zinc binding in peptide models of angiotensin-I converting enzyme active sites studied through 1H-NMR and chemical shift perturbation mapping.
  Biopolymers, 69, 244-252.  
14559923 D.R.Brooks, P.J.Appleford, L.Murray, and R.E.Isaac (2003).
An essential role in molting and morphogenesis of Caenorhabditis elegans for ACN-1, a novel member of the angiotensin-converting enzyme family that lacks a metallopeptidase active site.
  J Biol Chem, 278, 52340-52346.  
12914653 J.F.Riordan (2003).
Angiotensin-I-converting enzyme and its relatives.
  Genome Biol, 4, 225.  
12915047 K.Brew (2003).
Structure of human ACE gives new insights into inhibitor binding and design.
  Trends Pharmacol Sci, 24, 391-394.  
14668810 K.R.Acharya, E.D.Sturrock, J.F.Riordan, and M.R.Ehlers (2003).
Ace revisited: a new target for structure-based drug design.
  Nat Rev Drug Discov, 2, 891-902.  
12832763 M.Selkti, A.Tomas, J.F.Gaucher, T.Prangé, M.C.Fournié-Zaluski, H.Chen, and B.P.Roques (2003).
Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.
  Acta Crystallogr D Biol Crystallogr, 59, 1200-1205.
PDB codes: 1no0 1os0
12605218 N.M.Hooper, and A.J.Turner (2003).
An ACE structure.
  Nat Struct Biol, 10, 155-157.  
14526382 R.J.Lewis, and M.L.Garcia (2003).
Therapeutic potential of venom peptides.
  Nat Rev Drug Discov, 2, 790-802.  
12886014 S.Cal, V.Quesada, C.Garabaya, and C.Lopez-Otin (2003).
Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product.
  Proc Natl Acad Sci U S A, 100, 9185-9190.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.