8GKW: Serine hydroxymethyltransferase, mitochondrial

Human mitochondrial serine hydroxymethyltransferase (SHMT2) in complex with PLP, glycine and AGF359 inhibitor. Determined by X-ray diffraction at 2.38 Å resolution. Released 20 Mar 2024.

Method: X-ray diffraction
Resolution: 2.38 Å
Organism: Homo sapiens
Chains: 2
Atoms: 7,510
Mol. weight: 110.32 kDa
Ligands: PLP, ZVR, GLY
Released: 20 Mar 2024

Explore 8GKW in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8GKW contains 46 α-helices and 44 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 23 helices, 23 β-strands

Element	Residues	Length	Sheet
α-helix	49-52	4
α-helix	54-69	16
β-strand	71-72	2	1
α-helix	82-88	7
α-helix	91-94	4
β-strand	99-100	2	2
β-strand	103-104	2	2
α-helix	110-126	17
β-strand	134-137	4	3
α-helix	143-154	12
β-strand	160-162	3	3
β-strand	164	1	4
α-helix	166-168	3
α-helix	172-174	3
β-strand	177	1	5
β-strand	182	1	5
α-helix	185-187	3
β-strand	191-192	2	3
β-strand	195	1	4
β-strand	197-198	2	6
β-strand	203-204	2	6
α-helix	206-216	11
β-strand	220-223	4	3
α-helix	234-244	11
β-strand	247-251	5	3
α-helix	256-260	5
α-helix	267-269	3
β-strand	273-277	5	3
α-helix	280-282	3
β-strand	288-293	6	3
β-strand	296	1	7
β-strand	299	1	7
α-helix	303-308	6
α-helix	309-314	6
α-helix	320-333	14
α-helix	336-358	23
β-strand	362-363	2	8
β-strand	372-376	5	8
α-helix	384-393	10
β-strand	396-397	2	1
β-strand	399-401	3	8
β-strand	413-417	5	8
α-helix	419-423	5
α-helix	428-450	23
α-helix	455-464	10
α-helix	466-484	19

Chain B: 23 helices, 21 β-strands

Element	Residues	Length	Sheet
α-helix	49-52	4
α-helix	54-69	16
β-strand	71-72	2	9
α-helix	82-88	7
α-helix	91-94	4
β-strand	99-100	2	10
β-strand	103-104	2	10
α-helix	110-126	17
β-strand	134-137	4	11
α-helix	143-154	12
β-strand	160-164	5	11
α-helix	172-174	3
β-strand	177	1	12
β-strand	182	1	12
α-helix	185-189	5
β-strand	191-195	5	11
β-strand	197	1	13
β-strand	204	1	13
α-helix	206-216	11
β-strand	220-224	5	11
α-helix	234-244	11
β-strand	247-251	5	11
α-helix	256-260	5
α-helix	267-269	3
β-strand	273-277	5	11
α-helix	280-282	3
β-strand	288-293	6	11
β-strand	296	1	14
β-strand	301	1	14
α-helix	305-310	6
α-helix	311-316	6
α-helix	322-334	13
α-helix	338-359	22
β-strand	364-365	2	15
β-strand	374-378	5	15
α-helix	380-382	3
α-helix	386-394	9
β-strand	398-399	2	9
β-strand	401-403	3	15
β-strand	415-419	5	15
α-helix	421-424	4
α-helix	430-453	24
α-helix	457-466	10
α-helix	468-486	19

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Serine hydroxymethyltransferase, mitochondrial	A, B	protein	493	Homo sapiens	P34897 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8GKW_1 Serine hydroxymethyltransferase, mitochondrial (chains A, B)
MGSSHHHHHHSSGLVPRSNAAQTQTGEANRGWTGQESLSDSDPEMWELLQREKDRQCRGL
ELIASENFCSRAALEALGSCLNNKYSEGYPGKRYYGGAEVVDEIELLCQRRALEAFDLDP
AQWGVNVQPYSGSPANLAVYTALLQPHDRIMGLDLPDGGHLTHGYMSDVKRISATSIFFE
SMPYKLNPKTGLIDYNQLALTARLFRPRLIIAGTSAYARLIDYARMREVCDEVKAHLLAD
MAHISGLVAAKVIPSPFKHADIVTTTTHKTLRGARSGLIFYRKGVKAVDPKTGREIPYTF
EDRINFAVFPSLQGGPHNHAIAAVAVALKQACTPMFREYSLQVLKNARAMADALLERGYS
LVSGGTDNHLVLVDLRPKGLDGARAERVLELVSITANKNTCPGDRSAITPGGLRLGAPAL
TSRQFREDDFRRVVDFIDEGVNIGLEVKSKTAKLQDFKSFLLKDSETSQRLANLRQRVEQ
FARAFPMPGFDEH

Ligands and cofactors

ID	Name	Formula	Copies
PLP	Pyridoxal-5'-phosphate	C8 H10 N O6 P	2
ZVR	N-{4-[3-(2-amino-4-oxo-3,4-dihydro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)propyl]-2-fl…	C21 H22 F N5 O6	1
GLY	Glycine	C2 H5 N O2	2

Primary citation

Structural Characterization of 5-Substituted Pyrrolo[3,2- d ]pyrimidine Antifolate Inhibitors in Complex with Human Serine Hydroxymethyl Transferase 2. Katinas, J.M., Nayeen, M.J., Schneider, M. et al. Biochemistry (2024). DOI 10.1021/acs.biochem.3c00613 · PubMed

Other PDB entries of the same protein (UniProt P34897 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8AQL 1.23 Å, High-resolution crystal structure of human SHMT2
29LK 1.26 Å, High-resolution structure of human SHMT2 in complex with PLP-Ser (external aldimine)
9RWD 1.3 Å, High-resolution structure of human SHMT2 with covalently bound PLP (internal aldimine)
32JY 1.8 Å, Structure of the pathogenic variant G423S of Human SHMT2
6DK3 2.04 Å, Human mitochondrial serine hydroxymethyltransferase 2
9BOX 2.1 Å, Room-temperature X-ray structure of human mitochondrial serine hydroxymethyltransferase…
32JA 2.2 Å, Structure of the pathogenic variant T186R of Human SHMT2 in the apo open dimeric…
6QVL 2.28 Å, Human SHMT2 in complex with pemetrexed
6M5O 2.3 Å, Co-crystal structure of human serine hydroxymethyltransferase 2 in complex with…
6QVG 2.32 Å, Human SHMT2 in complex with lometrexol
5V7I 2.47 Å, Crystal structure of homo sapiens serine hydroxymethyltransferase 2 (mitochondrial)…
8FJT 2.47 Å, Human mitochondrial serine hydroxymethyltransferase (SHMT2) in complex with PLP, glycine…

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