hutI (PA5092, Q9HU91) notes

Identity

• UniProt Q9HU91 (HUTI_PSEAE), 402 aa, Swiss-Prot reviewed but PE 3 (inferred from
  homology). All functional annotation in the entry is HAMAP-Rule MF_00372 based
  [file:PSEAE/hutI/hutI-uniprot.txt "Catalyzes the hydrolytic cleavage of the carbon-nitrogen bond
  in imidazolone-5-propanoate to yield N-formimidoyl-L-glutamate"].
• Family: metallo-dependent hydrolase (amidohydrolase) superfamily, HutI family
  (HAMAP MF_00372, NCBIfam TIGR01224 hutI, InterPro IPR005920, PANTHER PTHR42752).
  HAMAP predicts metal ligands at 66, 68, 236, 311 and substrate/product contacts at 75,
  138, 171, 239, 313, 315, 316.
• Located in the PAO1 hut cluster (PA5091 hutG ... PA5106 hutF), next to hutG (PA5091).

Biology (literature)

• HutI is the third enzyme of the universal histidine degradation pathway, hydrolysing
  4-imidazolone-5-propanoate to N-formimino-L-glutamate (FIGLU)
  PMID:16990261.
  The B. subtilis HutI crystal structure shows a TIM-barrel amidohydrolase fold with a
  zinc ion in the active site and a substrate analog bound beside it
  PMID:16990261.
  A further structure exists for A. tumefaciens HutI (PMID:17640072, abstract not available).
• In P. aeruginosa the first three steps are catalysed by HutH, HutU and HutI
  PMID:16475788.
  Downstream, FIGLU is degraded by two branches (HutE four-step; HutF/HutG five-step)
  PMID:22225844.
  The HutI step is common to both branches
  PMID:17717196.
• hutI sits in the HutC-repressed hutU-hutG operon, which is induced by urocanate (PMID:41641996;
  PMID:17717196 for P. fluorescens).
• I found no P. aeruginosa paper that assays imidazolonepropionase in PAO1 extracts, or that
  reports a hutI mutant. Imidazolonepropionase is rarely assayed directly because its
  substrate is unstable. This is my own background knowledge, not a cited fact.

PMID:4290562 (Lessie & Neidhardt 1967), the PseudoCAP seed reference

• Abstract only. PMC276695 is a scanned article. MCP full text came back empty, and the
  PMC PDF is behind a browser challenge, so I could not read the full text.
• The abstract names the enzymes it studied: histidase (step I), urocanase (step II) and
  FIGLU degradation (step IV)
  PMID:4290562.
  Step III, imidazolonepropionase, is the only step it does not mention. The abstract
  describes urocanase-deficient mutants, a histidine auxotroph, and catabolite-repression
  mutants, but no step III mutant.
• The paper predates gene cloning, so it cannot link any activity to PA5092. Nothing
  visible in the abstract supports "imidazolonepropionase activity" or an IMP for hutI in
  "L-histidine catabolic process", but because that rests on the abstract's silence the
  reference defects are recorded as SUSPECTED. The claims themselves are almost certainly true; the
  reference is what fails to support them.

PseudoCAP IBA-seed assessment

Leaf IBAs from this node include human AMDHD1 and mouse/rat Amdhd1, so the single
PseudoCAP seed supports the imidazolonepropionase IBAs on mammals too.

Decisions summary

• ACCEPT: imidazolonepropionase activity (IBA, IEA, IMP), L-histidine catabolic process
  (IBA, IEA, IMP), cytoplasm (IEA).
• IMP rows are accepted on independent evidence (HAMAP family, structural homologs,
  operon context). Each carries a PSEUDOCAP source defect (WRONG_REFERENCE, CHECK, PROBABLE)
  because the cited abstract does not cover step III.
• The IBA MF row carries a GO_CENTRAL CHECK defect (SUSPECTED): the IBD at PTN000505272
  rests solely on this seed.
• MODIFY to GO:0050480: hydrolase activity; hydrolase activity acting on C-N (non-peptide)
  bonds; same in cyclic amides (all IEA, correct but general).
• KEEP_AS_NON_CORE: zinc ion binding, iron ion binding (HAMAP cofactor, Zn or Fe).

Full-text check of PMID:4290562 (2026-11-05)

The full text of Lessie and Neidhardt 1967 (J Bacteriol 93, 1800-1810) was supplied by the user and read. Its mutants are a urocanase-deficient strain, a histidine auxotroph and regulatory mutants with altered repression. Steps I, II and IV are assayed; imidazolonepropionase (step III) is never assayed and there is no hutI mutant. Both WRONG_REFERENCE defects on the IMP rows are now CONFIRMED and the reference is marked MISCITED.

PANTHER tree check (2026-11-05)

Topology fetched with projects/PSEUDOCAP/panther_tree.py node PTN000505272 --depth 2 --leaves (PTHR42752).

All 52 leaves sit in one subfamily (PTHR42752:SF1) and every one is named
imidazolonepropionase or probable imidazolonepropionase. There is no heterogeneous
child clade and no leaf that lacks the family signature, so the earlier worry about the
breadth of a LUCA-level node does not hold: GO:0050480 and GO:0006548 are right for the
whole clade. What the tree cannot fix is the IBD's evidential anchor, and the full text
of PMID:4290562 (read 2026-11-05) settles that separately: it assays no step III and has
no hutI mutant. The GO_CENTRAL defect is therefore kept, narrowed explicitly to the
citation, and raised SUSPECTED -> CONFIRMED. The tree also supplies the remedy: P42084
(B. subtilis HutI, solved structure) and Q96NU7 (human AMDHD1) are leaves of this node,
so a properly grounded IBD is available without moving the node. Annotation actions in
this review are unchanged (the IBA rows stay ACCEPT).