Np mrd loader

Showing NP-Card for 7-Methyladenine (NP0001095)

Jump To Section:
IdentificationSpectraBioTaxonomyChemoTaxonomyPhysical propertiesLinksReferencesXML
Record Information
Version2.0
Created at2009-01-29 15:21:03 UTC
Updated at2021-06-30 02:06:18 UTC
NP-MRD IDNP0001095
Secondary Accession NumbersNone
Natural Product Identification
Common Name7-Methyladenine
Description7-Methyladenine is part of the base excision repair pathway. In this pathway, alkylated DNA is hydrolysed via the enzyme DNA-3-methyladenine glycosylase II (EC 3.2.2.21), Releasing 3-methyladenine, 3-methylguanine, 7-methylguanine and 7-methyladenine. This enzyme is responsible for the hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions. Base excision repair (BER) is a cellular mechanism that repairs damaged DNA throughout the cell cycle. Repairing DNA sequence errors is necessary so that mutations are not propagated or to remove lesions that may lead to breaks in the DNA during replication. Single bases in DNA can be chemically mutated, for example by deamination or alkylation, resulting in incorrect base-pairing, and consequently, mutations in the DNA. Base excision repair involves flipping the mutated base out of the DNA helix and repairing the base alone. There are two main enzymes used, DNA glycosylases and AP endonucleases. The DNA glycosylase is used to break the beta-N glycosidic bond to create an AP site. AP endonuclease recognizes this site and nicks the damaged DNA on the 5' side (upstream) of the AP site creating a free 3'-OH. DNA polymerase, Pol I (human pol beta), extends the DNA from the free 3'-OH using its exonuclease activity to replace the nucleotide of the damaged base, as well as a few downstream, followed by sealing of the new DNA strand by DNA ligase. In mammalian cells, this is done by LigIII in complex with the scaffold protein XRCC1. Usually, BER is divided into short-patch repair (where a single nucleotide is replaced) or long-patch repair (where 2-10 nucleotides are replaced). Mammalian long-patch repair includes PCNA and pol delta/epsilon for nucleotide resynthesis, FEN1 to cut of the 'flap' including the damaged base, and LigI.
Structure
Thumb
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for NP0001095 (7-Methyladenine )


  Mrv1652305271900012D          

 11 12  0  0  0  0            999 V2000
   12.7517   -3.3548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7517   -4.1798    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -2.9423    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -4.5923    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3227   -3.3548    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3227   -4.1798    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5364   -3.0999    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.0212   -3.7673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5364   -4.4347    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -2.1173    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.7913   -2.3153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  3  1  2  0  0  0  0
  4  2  2  0  0  0  0
  5  3  1  0  0  0  0
  6  4  1  0  0  0  0
  6  5  2  0  0  0  0
  7  1  1  0  0  0  0
  2  1  1  0  0  0  0
  8  7  1  0  0  0  0
  9  8  2  0  0  0  0
  9  2  1  0  0  0  0
 10  3  1  0  0  0  0
 11  7  1  0  0  0  0
M  END
Download

3D MOL for NP0001095 (7-Methyladenine )

HMDB0011614
     RDKit          3D
7-Methyladenine
 18 19  0  0  0  0  0  0  0  0999 V2000
   -2.1683    0.3645   -0.1935 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0603   -0.5318   -0.1146 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1759   -1.8789   -0.1641 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0349   -2.4574   -0.0663 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9616   -1.4890    0.0489 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3096   -1.4613    0.1770 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9896   -0.3024    0.2744 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3062    0.8561    0.2430 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9516    0.8931    0.1162 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2428    2.1128    0.0842 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.2608   -0.3013    0.0168 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9945   -0.1109   -0.7856 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9550    1.3206   -0.6859 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6332    0.5874    0.8076 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1047   -2.4357   -0.2677 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.0775   -0.3032    0.3771 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1195    2.5462    0.9497 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.0768    2.5911   -0.8172 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  1  0
  9 11  2  0
 11  2  1  0
 11  5  1  0
  1 12  1  0
  1 13  1  0
  1 14  1  0
  3 15  1  0
  7 16  1  0
 10 17  1  0
 10 18  1  0
M  END
Download

3D SDF for NP0001095 (7-Methyladenine )


  Mrv1652305271900012D          

 11 12  0  0  0  0            999 V2000
   12.7517   -3.3548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7517   -4.1798    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -2.9423    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -4.5923    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3227   -3.3548    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3227   -4.1798    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5364   -3.0999    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.0212   -3.7673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5364   -4.4347    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.0373   -2.1173    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.7913   -2.3153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  3  1  2  0  0  0  0
  4  2  2  0  0  0  0
  5  3  1  0  0  0  0
  6  4  1  0  0  0  0
  6  5  2  0  0  0  0
  7  1  1  0  0  0  0
  2  1  1  0  0  0  0
  8  7  1  0  0  0  0
  9  8  2  0  0  0  0
  9  2  1  0  0  0  0
 10  3  1  0  0  0  0
 11  7  1  0  0  0  0
M  END
> <DATABASE_ID>
NP0001095

> <DATABASE_NAME>
NP-MRD

> <SMILES>
CN1C=NC2=NC=NC(N)=C12

> <INCHI_IDENTIFIER>
InChI=1S/C6H7N5/c1-11-3-10-6-4(11)5(7)8-2-9-6/h2-3H,1H3,(H2,7,8,9)

> <INCHI_KEY>
HCGHYQLFMPXSDU-UHFFFAOYSA-N

> <FORMULA>
C6H7N5

> <MOLECULAR_WEIGHT>
149.1533

> <EXACT_MASS>
149.070145249

> <JCHEM_ACCEPTOR_COUNT>
4

> <JCHEM_ATOM_COUNT>
18

> <JCHEM_AVERAGE_POLARIZABILITY>
14.288859624541752

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
1

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
7-methyl-7H-purin-6-amine

> <ALOGPS_LOGP>
-0.09

> <JCHEM_LOGP>
-0.34979416499999993

> <ALOGPS_LOGS>
-1.51

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
2

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA_STRONGEST_BASIC>
3.6000027949324966

> <JCHEM_POLAR_SURFACE_AREA>
69.62

> <JCHEM_REFRACTIVITY>
43.1162

> <JCHEM_ROTATABLE_BOND_COUNT>
0

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
4.66e+00 g/l

> <JCHEM_TRADITIONAL_IUPAC>
7-methyladenine

> <JCHEM_VEBER_RULE>
0

$$$$
Download

3D-SDF for NP0001095 (7-Methyladenine )

HMDB0011614
     RDKit          3D
7-Methyladenine
 18 19  0  0  0  0  0  0  0  0999 V2000
   -2.1683    0.3645   -0.1935 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0603   -0.5318   -0.1146 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1759   -1.8789   -0.1641 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0349   -2.4574   -0.0663 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9616   -1.4890    0.0489 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3096   -1.4613    0.1770 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9896   -0.3024    0.2744 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3062    0.8561    0.2430 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9516    0.8931    0.1162 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2428    2.1128    0.0842 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.2608   -0.3013    0.0168 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9945   -0.1109   -0.7856 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9550    1.3206   -0.6859 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6332    0.5874    0.8076 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1047   -2.4357   -0.2677 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.0775   -0.3032    0.3771 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1195    2.5462    0.9497 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.0768    2.5911   -0.8172 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  1  0
  9 11  2  0
 11  2  1  0
 11  5  1  0
  1 12  1  0
  1 13  1  0
  1 14  1  0
  3 15  1  0
  7 16  1  0
 10 17  1  0
 10 18  1  0
M  END
Download

PDB for NP0001095 (7-Methyladenine )

HEADER    PROTEIN                                 27-MAY-19   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   27-MAY-19         0                                  
HETATM    1  C   UNK     0      23.803  -6.262   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0      23.803  -7.802   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0      22.470  -5.492   0.000  0.00  0.00           C+0
HETATM    4  N   UNK     0      22.470  -8.572   0.000  0.00  0.00           N+0
HETATM    5  N   UNK     0      21.136  -6.262   0.000  0.00  0.00           N+0
HETATM    6  C   UNK     0      21.136  -7.802   0.000  0.00  0.00           C+0
HETATM    7  N   UNK     0      25.268  -5.786   0.000  0.00  0.00           N+0
HETATM    8  C   UNK     0      26.173  -7.032   0.000  0.00  0.00           C+0
HETATM    9  N   UNK     0      25.268  -8.278   0.000  0.00  0.00           N+0
HETATM   10  N   UNK     0      22.470  -3.952   0.000  0.00  0.00           N+0
HETATM   11  C   UNK     0      25.744  -4.322   0.000  0.00  0.00           C+0
CONECT    1    3    7    2                                                  
CONECT    2    4    1    9                                                  
CONECT    3    1    5   10                                                  
CONECT    4    2    6                                                       
CONECT    5    3    6                                                       
CONECT    6    4    5                                                       
CONECT    7    1    8   11                                                  
CONECT    8    7    9                                                       
CONECT    9    8    2                                                       
CONECT   10    3                                                            
CONECT   11    7                                                            
MASTER        0    0    0    0    0    0    0    0   11    0   24    0
END
Download

3D PDB for NP0001095 (7-Methyladenine )

COMPND    HMDB0011614
HETATM    1  C1  UNL     1      -2.168   0.365  -0.194  1.00  0.00           C  
HETATM    2  N1  UNL     1      -1.060  -0.532  -0.115  1.00  0.00           N  
HETATM    3  C2  UNL     1      -1.176  -1.879  -0.164  1.00  0.00           C  
HETATM    4  N2  UNL     1       0.035  -2.457  -0.066  1.00  0.00           N  
HETATM    5  C3  UNL     1       0.962  -1.489   0.049  1.00  0.00           C  
HETATM    6  N3  UNL     1       2.310  -1.461   0.177  1.00  0.00           N  
HETATM    7  C4  UNL     1       2.990  -0.302   0.274  1.00  0.00           C  
HETATM    8  N4  UNL     1       2.306   0.856   0.243  1.00  0.00           N  
HETATM    9  C5  UNL     1       0.952   0.893   0.116  1.00  0.00           C  
HETATM   10  N5  UNL     1       0.243   2.113   0.084  1.00  0.00           N  
HETATM   11  C6  UNL     1       0.261  -0.301   0.017  1.00  0.00           C  
HETATM   12  H1  UNL     1      -2.994  -0.111  -0.786  1.00  0.00           H  
HETATM   13  H2  UNL     1      -1.955   1.321  -0.686  1.00  0.00           H  
HETATM   14  H3  UNL     1      -2.633   0.587   0.808  1.00  0.00           H  
HETATM   15  H4  UNL     1      -2.105  -2.436  -0.268  1.00  0.00           H  
HETATM   16  H5  UNL     1       4.077  -0.303   0.377  1.00  0.00           H  
HETATM   17  H6  UNL     1      -0.119   2.546   0.950  1.00  0.00           H  
HETATM   18  H7  UNL     1       0.077   2.591  -0.817  1.00  0.00           H  
CONECT    1    2   12   13   14
CONECT    2    3   11
CONECT    3    4    4   15
CONECT    4    5
CONECT    5    6    6   11
CONECT    6    7
CONECT    7    8    8   16
CONECT    8    9
CONECT    9   10   11   11
CONECT   10   17   18
END
Download

SMILES for NP0001095 (7-Methyladenine )

CN1C=NC2=NC=NC(N)=C12
Download

INCHI for NP0001095 (7-Methyladenine )

InChI=1S/C6H7N5/c1-11-3-10-6-4(11)5(7)8-2-9-6/h2-3H,1H3,(H2,7,8,9)
Download
View in JSmol
Synonyms
ValueSource
6-Amino-7-methylpurineHMDB
7-Methyl-7H-purin-6-amineHMDB
7-Methyl-7H-purin-6-amine (acd/name 4.0)HMDB
7-Methyl-7H-purin-6-ylamine (acd/name 4.0)HMDB
7-Methyl-N7-methyladenineHMDB
7-MethyladenineChEMBL, HMDB
Chemical FormulaC6H7N5
Average Mass149.1533 Da
Monoisotopic Mass149.07015 Da
IUPAC Name7-methyl-7H-purin-6-amine
Traditional Name7-methyladenine
CAS Registry Number935-69-3
SMILES
CN1C=NC2=NC=NC(N)=C12
InChI Identifier
InChI=1S/C6H7N5/c1-11-3-10-6-4(11)5(7)8-2-9-6/h2-3H,1H3,(H2,7,8,9)
InChI KeyHCGHYQLFMPXSDU-UHFFFAOYSA-N
Experimental Spectra
Spectrum TypeDescriptionDepositor EmailDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, simulated)V.dorna832021-09-05View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Predicted Spectra
Not Available
Chemical Shift Submissions
Spectrum TypeDescriptionDepositor EmailDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, simulated)varshavi.d26@gmail.comNot AvailableNot Available2021-07-27View Spectrum
Species
Species of Origin
Species NameSourceReference
Anas platyrhynchosFooDB
AnatidaeFooDB
Anser anserFooDB
Bison bisonFooDB
Bos taurusFooDB
Bos taurus X Bison bisonFooDB
Bubalus bubalisFooDB
Capra aegagrus hircusFooDB
CervidaeFooDB
Cervus canadensisFooDB
ColumbaFooDB
ColumbidaeFooDB
Dromaius novaehollandiaeFooDB
Equus caballusFooDB
Gallus gallusFooDB
Isodictya erinaceaLOTUS Database
Lagopus mutaFooDB
LeporidaeFooDB
Lepus timidusFooDB
Melanitta fuscaFooDB
Meleagris gallopavoFooDB
Numida meleagrisFooDB
OdocoileusFooDB
OryctolagusFooDB
Ovis ariesFooDB
PhasianidaeFooDB
Phasianus colchicusFooDB
Struthio camelusFooDB
Sus scrofaFooDB
Sus scrofa domesticaFooDB
Chemical Taxonomy
Description Belongs to the class of organic compounds known as 6-aminopurines. These are purines that carry an amino group at position 6. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct Parent6-aminopurines
Alternative Parents
Substituents
  • 6-aminopurine
  • Aminopyrimidine
  • N-substituted imidazole
  • Pyrimidine
  • Imidolactam
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Azacycle
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Primary amine
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.66 g/LALOGPS
logP-0.09ALOGPS
logP-0.35ChemAxon
logS-1.5ALOGPS
pKa (Strongest Basic)3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.62 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity43.12 m³·mol⁻¹ChemAxon
Polarizability14.29 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0011614
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB028319
KNApSAcK IDNot Available
Chemspider ID64663
KEGG Compound IDC02241
BioCyc IDCPD-13320
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound71593
PDB IDNot Available
ChEBI ID28921
Good Scents IDNot Available
References
General References
  1. Harroun SG, Zhang Y, Chen TH, Ku CR, Chang HT: Biomarkers of cigarette smoking and DNA methylating agents: Raman, SERS and DFT study of 3-methyladenine and 7-methyladenine. Spectrochim Acta A Mol Biomol Spectrosc. 2017 Apr 5;176:1-7. doi: 10.1016/j.saa.2016.12.012. Epub 2016 Dec 15. [PubMed:28061366 ]
  2. Michelson AZ, Chen M, Wang K, Lee JK: Gas-phase studies of purine 3-methyladenine DNA glycosylase II (AlkA) substrates. J Am Chem Soc. 2012 Jun 13;134(23):9622-33. doi: 10.1021/ja211960r. Epub 2012 May 31. [PubMed:22554094 ]
  3. Tokuda S, Fukuda T, Kobayashi Y, Tanaka M, Matsui T: Effect of the uncharged imidazolium moiety in adenine on endothelium-independent relaxation in the contracted thoracic aorta of Sprague-Dawley rats. Biosci Biotechnol Biochem. 2012;76(4):828-30. doi: 10.1271/bbb.110806. Epub 2012 Apr 7. [PubMed:22484931 ]
  4. von Kugelgen I, Schiedel AC, Hoffmann K, Alsdorf BB, Abdelrahman A, Muller CE: Cloning and functional expression of a novel Gi protein-coupled receptor for adenine from mouse brain. Mol Pharmacol. 2008 Feb;73(2):469-77. doi: 10.1124/mol.107.037069. Epub 2007 Nov 1. [PubMed:17975009 ]
  5. Gorzalka S, Vittori S, Volpini R, Cristalli G, von Kugelgen I, Muller CE: Evidence for the functional expression and pharmacological characterization of adenine receptors in native cells and tissues. Mol Pharmacol. 2005 Mar;67(3):955-64. doi: 10.1124/mol.104.006601. Epub 2004 Dec 16. [PubMed:15604413 ]
  6. Cohen B, Hare PM, Kohler B: Ultrafast excited-state dynamics of adenine and monomethylated adenines in solution: implications for the nonradiative decay mechanism. J Am Chem Soc. 2003 Nov 5;125(44):13594-601. doi: 10.1021/ja035628z. [PubMed:14583057 ]
  7. Birkeland NK, Anensen H, Knaevelsrud I, Kristoffersen W, Bjoras M, Robb FT, Klungland A, Bjelland S: Methylpurine DNA glycosylase of the hyperthermophilic archaeon Archaeoglobus fulgidus. Biochemistry. 2002 Oct 22;41(42):12697-705. doi: 10.1021/bi020334w. [PubMed:12379112 ]