Structure of PDB 2h2q Chain A

Receptor sequence

>2h2qA (length=514) Species: 5693 (Trypanosoma cruzi)

SLFKIRMPETVAEGTRLALRAFSLVVAVDERGGIGDGRSIPWNVPEDMKF
FRDVTTKLRGKNVKPSPAKRNAVVMGRKTWDSIPPKFRPLPGRLNVVLSS
TLTTQHLLDGLPDEEKRNLHADSIVAVNGGLEQALQLLASPNYTPSIETV
YCIGGGSVYAEALRPPCVHLLQAIYRTTIRASESSCSVFFRVPESGTEAA
AGIEWQRETISEELTSANGNETKYYFEKLIPRNREEEQYLSLVDRIIREG
NVKHDRTGVGTLSIFGAQMRFSLRNNRLPLLTTKRVFWRGVCEELLWFLR
GETYAKKLSDKGVHIWDDNGSRAFLDSRGLTEYEEMDLGPVYGFQWRHFG
AAYTHHDANYDGQGVDQIKAIVETLKTNPDDRRMLFTAWNPSALPRMALP
PCHLLAQFYVSNGELSCMLYQRSCDMGLGVPFNIASYALLTILIAKATGL
RPGELVHTLGDAHVYSNHVEPCNEQLKRVPRAFPYLVFRREREFLEDYEE
GDMEVIDYAPYPPI

3D structure

• PDB: 2h2q Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function.
• Chain: A
• Resolution: 2.4 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): D48 E295 W317 Y343 C403 R423 D426
• Catalytic site (residue number reindexed from 1): D47 E294 W316 Y342 C402 R422 D425
• Enzyme Commision number: 1.5.1.3: dihydrofolate reductase.
  2.1.1.45: thymidylate synthase.

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	NAP	A	V27 A28 I35 G38 R39 S40 I41 G77 R78 K79 T80 L99 S100 S101 T102 G130 G131 I154 G155 G156 G157 S158	V26 A27 I34 G37 R38 S39 I40 G76 R77 K78 T79 L98 S99 S100 T101 G129 G130 I153 G154 G155 G156 S157
BS02	DU	A	C403 H404 Q422 R423 S424 D426 N434 H464 Y466	C402 H403 Q421 R422 S423 D425 N433 H463 Y465

Gene Ontology

Molecular Function

• GO:0004146 dihydrofolate reductase activity
• GO:0004799 thymidylate synthase activity
• GO:0008168 methyltransferase activity
• GO:0016491 oxidoreductase activity
• GO:0016741 transferase activity, transferring one-carbon groups

Biological Process

• GO:0006231 dTMP biosynthetic process
• GO:0006730 one-carbon metabolic process
• GO:0009165 nucleotide biosynthetic process
• GO:0032259 methylation
• GO:0046654 tetrahydrofolate biosynthetic process

Cellular Component

• GO:0005739 mitochondrion
• GO:0005829 cytosol

External links

• PDB: RCSB:2h2q, PDBe:2h2q, PDBj:2h2q
• PDBsum: 2h2q
• PubMed: 18536013
• UniProt: Q27793|DRTS_TRYCR Bifunctional dihydrofolate reductase-thymidylate synthase